2017 |
Harris, D; Lukoyanov, D; Shaw, S; Compton, P D; Tokmina-Lukaszewska, M; Bothner, B; Kelleher, N L; Dean, D R; Hoffman, B M; Seefeldt, L C The Mechanism of N2 Reduction Catalyzed by Fe-Nitrogenase Involves Reductive Elimination of H2 Journal Article Biochemistry, 2017. Abstract | Links | BibTeX | Tags: @article{Harris2017, title = {The Mechanism of N2 Reduction Catalyzed by Fe-Nitrogenase Involves Reductive Elimination of H2}, author = {D. Harris and D. Lukoyanov and S. Shaw and P.D. Compton and M. Tokmina-Lukaszewska and B. Bothner and N.L. Kelleher and D.R. Dean and B.M. Hoffman and L.C. Seefeldt}, url = {http://pubs.acs.org/doi/10.1021/acs.biochem.7b01142}, doi = {10.1021/acs.biochem.7b01142}, year = {2017}, date = {2017-12-28}, journal = {Biochemistry}, abstract = {Of the three forms of nitrogenase (Mo-nitrogenase, V-nitrogenase, and Fe-nitrogenase), the Fe-nitrogenase has the poorest ratio of N2 reduction relative to H2 evolution. Recent work on the Mo-nitrogenase has revealed that reductive elimination of two bridging Fe-H-Fe hydrides on the active site FeMo-cofactor to yield H2 is a key feature in the N2 reduction mechanism. The N2 reduction mechanism for the Fe-nitrogenase active site FeFe-cofactor was unknown. Here, we have purified both component proteins of the Fe-nitrogenase system, the electron-delivery Fe protein (AnfH) plus the catalytic FeFe protein (AnfDGK), and established its mechanism of N2 reduction. Inductively coupled plasma emission spectroscopy and protein mass spectrometry show that the FeFe protein component does not contain significant amounts of Mo or V, thus ruling out a requirement of these metals for N2 reduction. The fully functioning Fe-nitrogenase system was found to have specific activities for N2 reduction (1 atm) of 181 ± 5 nmol NH3 min-1 mg-1 FeFe protein, for proton reduction (in the absence of N2) of 1085 ± 41 nmol H2 min-1 mg-1 FeFe protein, and for acetylene reduction (0.3 atm) of 306 ± 3 nmol C2H4 min-1 mg-1 FeFe protein. Under turnover conditions N2 reduction is inhibited by H2 and the enzyme catalyzes the formation of HD when presented with N2 and D2. These observations are explained by the accumulation of four reducing equivalents as two metal-bound hydrides and two protons at the FeFe-cofactor, with activation for N2 reduction occurring by reductive elimination of H2.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Of the three forms of nitrogenase (Mo-nitrogenase, V-nitrogenase, and Fe-nitrogenase), the Fe-nitrogenase has the poorest ratio of N2 reduction relative to H2 evolution. Recent work on the Mo-nitrogenase has revealed that reductive elimination of two bridging Fe-H-Fe hydrides on the active site FeMo-cofactor to yield H2 is a key feature in the N2 reduction mechanism. The N2 reduction mechanism for the Fe-nitrogenase active site FeFe-cofactor was unknown. Here, we have purified both component proteins of the Fe-nitrogenase system, the electron-delivery Fe protein (AnfH) plus the catalytic FeFe protein (AnfDGK), and established its mechanism of N2 reduction. Inductively coupled plasma emission spectroscopy and protein mass spectrometry show that the FeFe protein component does not contain significant amounts of Mo or V, thus ruling out a requirement of these metals for N2 reduction. The fully functioning Fe-nitrogenase system was found to have specific activities for N2 reduction (1 atm) of 181 ± 5 nmol NH3 min-1 mg-1 FeFe protein, for proton reduction (in the absence of N2) of 1085 ± 41 nmol H2 min-1 mg-1 FeFe protein, and for acetylene reduction (0.3 atm) of 306 ± 3 nmol C2H4 min-1 mg-1 FeFe protein. Under turnover conditions N2 reduction is inhibited by H2 and the enzyme catalyzes the formation of HD when presented with N2 and D2. These observations are explained by the accumulation of four reducing equivalents as two metal-bound hydrides and two protons at the FeFe-cofactor, with activation for N2 reduction occurring by reductive elimination of H2. |
Rickels, R; Herz, H M; Sze, C C; Cao, K; Morgan, M A; Collings, C K; Gause, M; Takahashi, Y H; Wang, L; Rendleman, E J; Marshall, S A; Krueger, A; Bartom, E T; A. Piunti, ; Smith, E R; Abshiru, N A; Kelleher, N L; Dorsett, D; A.Shilatifard, Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability. Journal Article Nat. Genet., 49 (11), pp. 1647-1653, 2017. Abstract | Links | BibTeX | Tags: @article{Rickels2017, title = {Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability.}, author = {R. Rickels and H.M. Herz and C.C. Sze and K. Cao and M.A. Morgan and C.K. Collings and M. Gause and Y.H. Takahashi and L. Wang and E.J. Rendleman and S.A. Marshall and A. Krueger and E.T. Bartom and A. Piunti, and E.R. Smith and N.A. Abshiru and N.L. Kelleher and D. Dorsett and A.Shilatifard}, url = {https://www.nature.com/articles/ng.3965}, doi = {10.1038/ng.3965}, year = {2017}, date = {2017-11-30}, journal = {Nat. Genet.}, volume = {49}, number = {11}, pages = {1647-1653}, abstract = {Histone H3 lysine 4 monomethylation (H3K4me1) is an evolutionarily conserved feature of enhancer chromatin catalyzed by the COMPASS-like methyltransferase family, which includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals. Here we demonstrate that Drosophila embryos expressing catalytically deficient Trr eclose and develop to productive adulthood. Parallel experiments with a trr allele that augments enzyme product specificity show that conversion of H3K4me1 at enhancers to H3K4me2 and H3K4me3 is also compatible with life and results in minimal changes in gene expression. Similarly, loss of the catalytic SET domains of MLL3 and MLL4 in mouse embryonic stem cells (mESCs) does not disrupt self-renewal. Drosophila embryos with trr alleles encoding catalytic mutants manifest subtle developmental abnormalities when subjected to temperature stress or altered cohesin levels. Collectively, our findings suggest that animal development can occur in the context of Trr or mammalian COMPASS-like proteins deficient in H3K4 monomethylation activity and point to a possible role for H3K4me1 on cis-regulatory elements in specific settings to fine-tune transcriptional regulation in response to environmental stress.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Histone H3 lysine 4 monomethylation (H3K4me1) is an evolutionarily conserved feature of enhancer chromatin catalyzed by the COMPASS-like methyltransferase family, which includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals. Here we demonstrate that Drosophila embryos expressing catalytically deficient Trr eclose and develop to productive adulthood. Parallel experiments with a trr allele that augments enzyme product specificity show that conversion of H3K4me1 at enhancers to H3K4me2 and H3K4me3 is also compatible with life and results in minimal changes in gene expression. Similarly, loss of the catalytic SET domains of MLL3 and MLL4 in mouse embryonic stem cells (mESCs) does not disrupt self-renewal. Drosophila embryos with trr alleles encoding catalytic mutants manifest subtle developmental abnormalities when subjected to temperature stress or altered cohesin levels. Collectively, our findings suggest that animal development can occur in the context of Trr or mammalian COMPASS-like proteins deficient in H3K4 monomethylation activity and point to a possible role for H3K4me1 on cis-regulatory elements in specific settings to fine-tune transcriptional regulation in response to environmental stress. |
S.Turcan, ; V.Makarov, ; J.Taranda, ; Y.Wang, ; Fabius, A W M; W.Wu, ; Y.Zheng, ; N.El-Amine, ; S.Haddock, ; G.Nanjangud, ; H.C.LeKaye, ; C.Brennan, ; J.Cross, ; J.T.Huse, ; Kelleher, N L; P.Osten, ; C.B.Thompson, ; T.A.Chan, Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence. Journal Article Nat. Genet., 2017. Abstract | Links | BibTeX | Tags: @article{S.Turcan2017, title = {Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.}, author = {S.Turcan and V.Makarov and J.Taranda and Y.Wang and A.W.M. Fabius and W.Wu and Y.Zheng and N.El-Amine and S.Haddock and G.Nanjangud and H.C.LeKaye and C.Brennan and J.Cross and J.T.Huse and N.L. Kelleher and P.Osten and C.B.Thompson and T.A.Chan}, url = {https://www.nature.com/articles/s41588-017-0001-z}, doi = {10.1038/s41588-017-0001-z}, year = {2017}, date = {2017-11-27}, journal = {Nat. Genet.}, abstract = {Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24+ population with a proliferative advantage and stem-like transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations. Together, these observations provide unprecedented high-resolution molecular portraits of mutant-IDH1-dependent epigenomic reprogramming. These findings have substantial implications for understanding of mutant IDH function and for optimizing therapeutic approaches to targeting IDH-mutant tumors.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24+ population with a proliferative advantage and stem-like transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations. Together, these observations provide unprecedented high-resolution molecular portraits of mutant-IDH1-dependent epigenomic reprogramming. These findings have substantial implications for understanding of mutant IDH function and for optimizing therapeutic approaches to targeting IDH-mutant tumors. |
Skinner, O S; Haverland, N A; Fornelli, L; Melani, R D; Vale, Do L H F; Seckler, H S; Doubleday, P F; Schachner, L F; Srzentić, K; Kelleher, N L; Compton, P D Top-down characterization of endogenous protein complexes with native proteomics. Journal Article Nat. Chem. Biol., 2017. Abstract | Links | BibTeX | Tags: @article{Skinner2017, title = {Top-down characterization of endogenous protein complexes with native proteomics.}, author = {O.S. Skinner and N.A. Haverland and L. Fornelli and R.D. Melani and L.H.F. Do Vale and H.S. Seckler and P.F. Doubleday and L.F. Schachner and K. Srzentić and N.L. Kelleher and P.D. Compton}, url = {https://www.nature.com/articles/nchembio.2515}, doi = {10.1038/nchembio.2515}, year = {2017}, date = {2017-11-13}, journal = {Nat. Chem. Biol.}, abstract = {Protein complexes exhibit great diversity in protein membership, post-translational modifications and noncovalent cofactors, enabling them to function as the actuators of many important biological processes. The exposition of these molecular features using current methods lacks either throughput or molecular specificity, ultimately limiting the use of protein complexes as direct analytical targets in a wide range of applications. Here, we apply native proteomics, enabled by a multistage tandem MS approach, to characterize 125 intact endogenous complexes and 217 distinct proteoforms derived from mouse heart and human cancer cell lines in discovery mode. The native conditions preserved soluble protein-protein interactions, high-stoichiometry noncovalent cofactors, covalent modifications to cysteines, and, remarkably, superoxide ligands bound to the metal cofactor of superoxide dismutase 2. These data enable precise compositional analysis of protein complexes as they exist in the cell and demonstrate a new approach that uses MS as a bridge to structural biology.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Protein complexes exhibit great diversity in protein membership, post-translational modifications and noncovalent cofactors, enabling them to function as the actuators of many important biological processes. The exposition of these molecular features using current methods lacks either throughput or molecular specificity, ultimately limiting the use of protein complexes as direct analytical targets in a wide range of applications. Here, we apply native proteomics, enabled by a multistage tandem MS approach, to characterize 125 intact endogenous complexes and 217 distinct proteoforms derived from mouse heart and human cancer cell lines in discovery mode. The native conditions preserved soluble protein-protein interactions, high-stoichiometry noncovalent cofactors, covalent modifications to cysteines, and, remarkably, superoxide ligands bound to the metal cofactor of superoxide dismutase 2. These data enable precise compositional analysis of protein complexes as they exist in the cell and demonstrate a new approach that uses MS as a bridge to structural biology. |
Mascarenhas, R; Le, H V; Clevenger, K D; Lehrer, H J; Ringe, D; Kelleher, N L; Silverman, R B; Liu, D Biochemistry, 56 (43), pp. 5844-5845, 2017. @article{Mascarenhas2017b, title = {Correction to Selective Targeting by a Mechanism-Based Inactivator against Pyridoxal 5'-Phosphate-Dependent Enzymes: Mechanisms of Inactivation and Alternative Turnover.}, author = {R. Mascarenhas and H.V. Le and K.D. Clevenger and H.J. Lehrer and D. Ringe and N.L. Kelleher and R.B. Silverman and D. Liu}, url = {http://pubs.acs.org/doi/10.1021/acs.biochem.7b00961}, doi = {10.1021/acs.biochem.7b00961}, year = {2017}, date = {2017-10-31}, journal = {Biochemistry}, volume = {56}, number = {43}, pages = {5844-5845}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Skinner, O S; McAnally, M O; Duyne, Van R P; Schatz, G C; Breuker, K; Compton, P D; Kelleher, N L Native Electron Capture Dissociation Maps to Iron-Binding Channels in Horse Spleen Ferritin Journal Article Anal. Chem. , 89 (20), pp. 10711-10716, 2017. Abstract | Links | BibTeX | Tags: @article{Skinner2017b, title = {Native Electron Capture Dissociation Maps to Iron-Binding Channels in Horse Spleen Ferritin}, author = {O.S. Skinner and M.O. McAnally and R.P. Van Duyne and G.C. Schatz and K. Breuker and P.D. Compton and N.L. Kelleher}, url = {http://pubs.acs.org/doi/10.1021/acs.analchem.7b01581}, doi = {10.1021/acs.analchem.7b01581}, year = {2017}, date = {2017-10-17}, journal = {Anal. Chem. }, volume = {89}, number = {20}, pages = {10711-10716}, abstract = {Native electron capture dissociation (NECD) is a process during which proteins undergo fragmentation similar to that from radical dissociation methods, but without the addition of exogenous electrons. However, after three initial reports of NECD from the cytochrome c dimer complex, no further evidence of the effect has been published. Here, we report NECD behavior from horse spleen ferritin, a ∼490 kDa protein complex ∼20-fold larger than the previously studied cytochrome c dimer. Application of front-end infrared excitation (FIRE) in conjunction with low- and high-m/z quadrupole isolation and collisionally activated dissociation (CAD) provides new insights into the NECD mechanism. Additionally, activation of the intact complex in either the electrospray droplet or the gas phase produced c-type fragment ions. Similar to the previously reported results on cytochrome c, these fragment ions form near residues known to interact with iron atoms in solution. By mapping the location of backbone cleavages associated with c-type ions onto the crystal structure, we are able to characterize two distinct iron binding channels that facilitate iron ion transport into the core of the complex. The resulting pathways are in good agreement with previously reported results for iron binding sites in mammalian ferritin.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Native electron capture dissociation (NECD) is a process during which proteins undergo fragmentation similar to that from radical dissociation methods, but without the addition of exogenous electrons. However, after three initial reports of NECD from the cytochrome c dimer complex, no further evidence of the effect has been published. Here, we report NECD behavior from horse spleen ferritin, a ∼490 kDa protein complex ∼20-fold larger than the previously studied cytochrome c dimer. Application of front-end infrared excitation (FIRE) in conjunction with low- and high-m/z quadrupole isolation and collisionally activated dissociation (CAD) provides new insights into the NECD mechanism. Additionally, activation of the intact complex in either the electrospray droplet or the gas phase produced c-type fragment ions. Similar to the previously reported results on cytochrome c, these fragment ions form near residues known to interact with iron atoms in solution. By mapping the location of backbone cleavages associated with c-type ions onto the crystal structure, we are able to characterize two distinct iron binding channels that facilitate iron ion transport into the core of the complex. The resulting pathways are in good agreement with previously reported results for iron binding sites in mammalian ferritin. |
Haverland, N A; Wass, M; Ntai, I; Keppel, T; Gundry, R L; Kelleher, N L Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes Journal Article Proteomics, 17 (19), 2017. Abstract | Links | BibTeX | Tags: @article{Haverland2017, title = {Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes}, author = {N.A. Haverland and M. Wass and I. Ntai and T. Keppel and R.L. Gundry and N.L. Kelleher}, url = {http://onlinelibrary.wiley.com/doi/10.1002/pmic.201700156/epdf}, doi = {10.1002/pmic.201700156}, year = {2017}, date = {2017-10-17}, journal = {Proteomics}, volume = {17}, number = {19}, abstract = {Lymphocytes are immune cells that are critical for the maintenance of adaptive immunity. Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lymphocytes are immune cells that are critical for the maintenance of adaptive immunity. Differentiation of lymphoid progenitors yields B-, T-, and NK-cell subtypes that individually correlate with specific forms of leukemia or lymphoma. Therefore, it is imperative a precise method of cell categorization is utilized to detect differences in distinct disease states present in patients. One viable means of classification involves evaluation of the cell surface proteome of lymphoid malignancies. Specifically, this manuscript details the use of an antibody independent approach known as Cell Surface Capture Technology, to assess the N-glycoproteome of four human lymphocyte cell lines. Altogether, 404 cell surface N-glycoproteins were identified as markers for specific cell types involved in lymphocytic malignancies, including 82 N-glycoproteins that had not been previously been described for B or T cells within the Cell Surface Protein Atlas. Comparative analysis, hierarchical clustering techniques, and label-free quantitation were used to reveal proteins most informative for each cell type. Undoubtedly, the characterization of the cell surface proteome of lymphoid malignancies is a first step toward improving personalized diagnosis and treatment of leukemia and lymphoma. |
Ezponda, T; Dupéré-Richer, D; Will, C M; Small, E C; Varghese, N; Patel, T; Nabet, B; Popovic, R; Oyer, J; Bulic, M; Zheng, Y; Huang, X; Shah, M Y; Maji, S; Riva, A; Occhionorelli, M; Tonon, G; Kelleher, N; Keats, J; Licht, J D UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition Journal Article Cell. Rep. , 21 (3), pp. 628-640, 2017. Abstract | Links | BibTeX | Tags: @article{Ezponda2017, title = {UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition}, author = {T. Ezponda and D. Dupéré-Richer and C.M. Will and E.C. Small and N. Varghese and T. Patel and B. Nabet and R. Popovic and J. Oyer and M. Bulic and Y. Zheng and X. Huang and M.Y. Shah and S. Maji and A. Riva and M. Occhionorelli and G. Tonon and N. Kelleher and J. Keats and J.D. Licht }, url = {http://www.sciencedirect.com/science/article/pii/S2211124717313839?via%3Dihub}, doi = {10.1016/j.celrep.2017.09.078}, year = {2017}, date = {2017-10-17}, journal = {Cell. Rep. }, volume = {21}, number = {3}, pages = {628-640}, abstract = {Loss or inactivation of the histone H3K27 demethylase UTX occurs in several malignancies, including multiple myeloma (MM). Using an isogenic cell system, we found that loss of UTX leads to deactivation of gene expression ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM cells. Moreover, UTX mutant cells showed increased in vitro and in vivo sensitivity to inhibition of EZH2, a histone methyltransferase that generates H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c-MYC and an activation of repressors of IRF4 characteristic of germinal center B cells such as BCL6 and IRF1. Rebalance of H3K27me3 levels at specific genes through EZH2 inhibitors may be a therapeutic strategy in MM cases harboring UTX mutations.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Loss or inactivation of the histone H3K27 demethylase UTX occurs in several malignancies, including multiple myeloma (MM). Using an isogenic cell system, we found that loss of UTX leads to deactivation of gene expression ultimately promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM cells. Moreover, UTX mutant cells showed increased in vitro and in vivo sensitivity to inhibition of EZH2, a histone methyltransferase that generates H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c-MYC and an activation of repressors of IRF4 characteristic of germinal center B cells such as BCL6 and IRF1. Rebalance of H3K27me3 levels at specific genes through EZH2 inhibitors may be a therapeutic strategy in MM cases harboring UTX mutations. |
Zha, L; Jiang, Y; Henke, M T; Wilson, M R; Wang, J X; Kelleher, N L; Balskus, E P Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring. Journal Article Nat Chem Biol, 13 (10), pp. 1063-1065, 2017. Abstract | Links | BibTeX | Tags: @article{Zha2017, title = {Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring.}, author = {L. Zha and Y. Jiang and M.T. Henke and M.R. Wilson and J.X. Wang and N.L. Kelleher and E.P. Balskus}, url = {http://dx.doi.org/10.1038/nchembio.2448}, doi = {10.1038/nchembio.2448}, year = {2017}, date = {2017-10-01}, journal = {Nat Chem Biol}, volume = {13}, number = {10}, pages = {1063-1065}, abstract = {Despite containing an α-amino acid, the versatile cofactor S-adenosylmethionine (SAM) is not a known building block for nonribosomal peptide synthetase (NRPS) assembly lines. Here we report an unusual NRPS module from colibactin biosynthesis that uses SAM for amide bond formation and subsequent cyclopropanation. Our findings showcase a new use for SAM and reveal a novel biosynthetic route to a functional group that likely mediates colibactin's genotoxicity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Despite containing an α-amino acid, the versatile cofactor S-adenosylmethionine (SAM) is not a known building block for nonribosomal peptide synthetase (NRPS) assembly lines. Here we report an unusual NRPS module from colibactin biosynthesis that uses SAM for amide bond formation and subsequent cyclopropanation. Our findings showcase a new use for SAM and reveal a novel biosynthetic route to a functional group that likely mediates colibactin's genotoxicity. |
Morgan, M A J; Rickels, R A; Collings, C K; He, X; Cao, K; Herz, H M; Cozzolino, K A; Abshiru, N A; Marshall, S A; Rendleman, E J; Sze, C C; Piunti, A; Kelleher, N L; Savas, J N; Shilatifard, A A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation. Journal Article Genes. Dev., 19 , pp. 2003-2014, 2017. Abstract | Links | BibTeX | Tags: @article{Morgan2017, title = {A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation.}, author = {M.A.J. Morgan and R.A. Rickels and C.K. Collings and X. He and K. Cao and H.M. Herz and K.A. Cozzolino and N.A. Abshiru and S.A. Marshall and E.J. Rendleman and C.C. Sze and A. Piunti and N.L. Kelleher and J.N. Savas and A. Shilatifard}, url = {http://genesdev.cshlp.org/content/31/19/2003.long}, doi = {10.1101/gad.305201.117.}, year = {2017}, date = {2017-10-01}, journal = {Genes. Dev.}, volume = {19}, pages = {2003-2014}, abstract = {Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4-RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain. Using CRISPR-Cas9 genetic knockouts, we demonstrate that COMPASS H3K4 methyltransferase family members differentially regulate BRWD2/PHIP chromatin occupancy. Finally, we demonstrate that depletion of the single Drosophila homolog dBRWD3 results in altered gene expression and aberrant patterns of histone H3 Lys27 acetylation at enhancers and promoters, suggesting a cross-talk between these chromatin modifications and transcription through the BRWD protein family.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4-RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain. Using CRISPR-Cas9 genetic knockouts, we demonstrate that COMPASS H3K4 methyltransferase family members differentially regulate BRWD2/PHIP chromatin occupancy. Finally, we demonstrate that depletion of the single Drosophila homolog dBRWD3 results in altered gene expression and aberrant patterns of histone H3 Lys27 acetylation at enhancers and promoters, suggesting a cross-talk between these chromatin modifications and transcription through the BRWD protein family. |
Ichikawa, Y; Connelly, C F; Appleboim, A; Miller, T C; Jacobi, H; Abshiru, N A; Chou, H J; Chen, Y; Sharma, U; Zheng, Y; Thomas, P M; Chen, H V; Bajaj, V; Müller, C W; Kelleher, N L; Friedman, N; Bolon, D N; Rando, O J; Kaufman, P D A synthetic biology approach to probing nucleosome symmetry Journal Article eLife, (6), 2017. Abstract | Links | BibTeX | Tags: @article{Ichikawa2017, title = {A synthetic biology approach to probing nucleosome symmetry}, author = {Y. Ichikawa and C.F. Connelly and A. Appleboim and T.C. Miller and H. Jacobi and N.A. Abshiru and H.J. Chou and Y. Chen and U. Sharma and Y. Zheng and P.M. Thomas and H.V. Chen and V. Bajaj and C.W. Müller and N.L. Kelleher and N. Friedman and D.N. Bolon and O.J. Rando and P.D. Kaufman}, url = {https://elifesciences.org/articles/28836}, doi = {10.7554/eLife.28836.}, year = {2017}, date = {2017-09-12}, journal = {eLife}, number = {6}, abstract = {The repeating subunit of chromatin, the nucleosome, includes two copies of each of the four core histones, and several recent studies have reported that asymmetrically-modified nucleosomes occur at regulatory elements in vivo. To probe the mechanisms by which histone modifications are read out, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, which we extensively validated genetically and biochemically. Comparing the effects of asymmetric histone tail point mutants with those of symmetric double mutants revealed that a single methylated H3K36 per nucleosome was sufficient to silence cryptic transcription in vivo. We also demonstrate the utility of this system for analysis of histone modification crosstalk, using mass spectrometry to separately identify modifications on each H3 molecule within asymmetric nucleosomes. The ability to generate asymmetric nucleosomes in vivo and in vitro provides a powerful and generalizable tool to probe the mechanisms by which H3 tails are read out by effector proteins in the cell.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The repeating subunit of chromatin, the nucleosome, includes two copies of each of the four core histones, and several recent studies have reported that asymmetrically-modified nucleosomes occur at regulatory elements in vivo. To probe the mechanisms by which histone modifications are read out, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, which we extensively validated genetically and biochemically. Comparing the effects of asymmetric histone tail point mutants with those of symmetric double mutants revealed that a single methylated H3K36 per nucleosome was sufficient to silence cryptic transcription in vivo. We also demonstrate the utility of this system for analysis of histone modification crosstalk, using mass spectrometry to separately identify modifications on each H3 molecule within asymmetric nucleosomes. The ability to generate asymmetric nucleosomes in vivo and in vitro provides a powerful and generalizable tool to probe the mechanisms by which H3 tails are read out by effector proteins in the cell. |
Mascarenhas, R; Le, H V; Clevenger, K D; Lehrer, H J; Ringe, D; Kelleher, N L; Silverman, R B; Liu, D Biochemistry, 56 (37), pp. 4951-4961, 2017. Abstract | Links | BibTeX | Tags: @article{Mascarenhas2017, title = {Selective Targeting by a Mechanism-Based Inactivator against Pyridoxal 5'-Phosphate-Dependent Enzymes: Mechanisms of Inactivation and Alternative Turnover.}, author = {R. Mascarenhas and H.V. Le and K.D. Clevenger and H.J. Lehrer and D. Ringe and N.L. Kelleher and R.B. Silverman and D. Liu}, url = {https://dx.doi.org/10.1021/acs.biochem.7b00499}, doi = {10.1021/acs.biochem.7b00499}, year = {2017}, date = {2017-09-06}, journal = {Biochemistry}, volume = {56}, number = {37}, pages = {4951-4961}, abstract = {Potent mechanism-based inactivators can be rationally designed against pyridoxal 5'-phosphate (PLP)-dependent drug targets, such as ornithine aminotransferase (OAT) or γ-aminobutyric acid aminotransferase (GABA-AT). An important challenge, however, is the lack of selectivity toward other PLP-dependent, off-target enzymes, because of similarities in mechanisms of all PLP-dependent aminotransferase reactions. On the basis of complex crystal structures, we investigate the inactivation mechanism of OAT, a hepatocellular carcinoma target, by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP), a known inactivator of GABA-AT. A crystal structure of OAT and FCP showed the formation of a ternary adduct. This adduct can be rationalized as occurring via an enamine mechanism of inactivation, similar to that reported for GABA-AT. However, the crystal structure of an off-target, PLP-dependent enzyme, aspartate aminotransferase (Asp-AT), in complex with FCP, along with the results of attempted inhibition assays, suggests that FCP is not an inactivator of Asp-AT, but rather an alternate substrate. Turnover of FCP by Asp-AT is also supported by high-resolution mass spectrometry. Amid existing difficulties in achieving selectivity of inactivation among a large number of PLP-dependent enzymes, the obtained results provide evidence that a desirable selectivity could be achieved, taking advantage of subtle structural and mechanistic differences between a drug-target enzyme and an off-target enzyme, despite their largely similar substrate binding sites and catalytic mechanisms.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Potent mechanism-based inactivators can be rationally designed against pyridoxal 5'-phosphate (PLP)-dependent drug targets, such as ornithine aminotransferase (OAT) or γ-aminobutyric acid aminotransferase (GABA-AT). An important challenge, however, is the lack of selectivity toward other PLP-dependent, off-target enzymes, because of similarities in mechanisms of all PLP-dependent aminotransferase reactions. On the basis of complex crystal structures, we investigate the inactivation mechanism of OAT, a hepatocellular carcinoma target, by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP), a known inactivator of GABA-AT. A crystal structure of OAT and FCP showed the formation of a ternary adduct. This adduct can be rationalized as occurring via an enamine mechanism of inactivation, similar to that reported for GABA-AT. However, the crystal structure of an off-target, PLP-dependent enzyme, aspartate aminotransferase (Asp-AT), in complex with FCP, along with the results of attempted inhibition assays, suggests that FCP is not an inactivator of Asp-AT, but rather an alternate substrate. Turnover of FCP by Asp-AT is also supported by high-resolution mass spectrometry. Amid existing difficulties in achieving selectivity of inactivation among a large number of PLP-dependent enzymes, the obtained results provide evidence that a desirable selectivity could be achieved, taking advantage of subtle structural and mechanistic differences between a drug-target enzyme and an off-target enzyme, despite their largely similar substrate binding sites and catalytic mechanisms. |
Wildburger, N C; Esparza, T J; LeDuc, R D; Fellers, R T; Thomas, P M; Cairns, N J; Kelleher, N L; Bateman, R J; Brody, D L Diversity of Amyloid-beta Proteoforms in the Alzheimer’s Disease Brain Journal Article Sci. Rep. , 7 (1), pp. 9520, 2017. Abstract | Links | BibTeX | Tags: @article{Wildburger2017, title = {Diversity of Amyloid-beta Proteoforms in the Alzheimer’s Disease Brain}, author = {N.C. Wildburger and T.J. Esparza and R.D. LeDuc and R.T. Fellers and P.M. Thomas and N.J. Cairns and N.L. Kelleher and R.J. Bateman and D.L. Brody}, url = {https://www.nature.com/articles/s41598-017-10422-x}, doi = {10.1038/s41598-017-10422-x}, year = {2017}, date = {2017-08-25}, journal = {Sci. Rep. }, volume = {7}, number = {1}, pages = {9520}, abstract = {Amyloid-beta (Aβ) plays a key role in the pathogenesis of Alzheimer's disease (AD), but little is known about the proteoforms present in AD brain. We used high-resolution mass spectrometry to analyze intact Aβ from soluble aggregates and insoluble material in brains of six cases with severe dementia and pathologically confirmed AD. The soluble aggregates are especially relevant because they are believed to be the most toxic form of Aβ. We found a diversity of Aβ peptides, with 26 unique proteoforms including various N- and C-terminal truncations. N- and C-terminal truncations comprised 73% and 30%, respectively, of the total Aβ proteoforms detected. The Aβ proteoforms segregated between the soluble and more insoluble aggregates with N-terminal truncations predominating in the insoluble material and C- terminal truncations segregating into the soluble aggregates. In contrast, canonical Aβ comprised the minority of the identified proteoforms (15.3%) and did not distinguish between the soluble and more insoluble aggregates. The relative abundance of many truncated Aβ proteoforms did not correlate with post-mortem interval, suggesting they are not artefacts. This heterogeneity of Aβ proteoforms deepens our understanding of AD and offers many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Amyloid-beta (Aβ) plays a key role in the pathogenesis of Alzheimer's disease (AD), but little is known about the proteoforms present in AD brain. We used high-resolution mass spectrometry to analyze intact Aβ from soluble aggregates and insoluble material in brains of six cases with severe dementia and pathologically confirmed AD. The soluble aggregates are especially relevant because they are believed to be the most toxic form of Aβ. We found a diversity of Aβ peptides, with 26 unique proteoforms including various N- and C-terminal truncations. N- and C-terminal truncations comprised 73% and 30%, respectively, of the total Aβ proteoforms detected. The Aβ proteoforms segregated between the soluble and more insoluble aggregates with N-terminal truncations predominating in the insoluble material and C- terminal truncations segregating into the soluble aggregates. In contrast, canonical Aβ comprised the minority of the identified proteoforms (15.3%) and did not distinguish between the soluble and more insoluble aggregates. The relative abundance of many truncated Aβ proteoforms did not correlate with post-mortem interval, suggesting they are not artefacts. This heterogeneity of Aβ proteoforms deepens our understanding of AD and offers many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development. |
Zhou, Y; Zhang, X; Fornelli, L; Compton, P D; Kelleher, N; Wirth, M J Chromatographic efficiency and selectivity in top-down proteomics of histones. Journal Article J Chromatogr B Analyt Technol Biomed Life Sci, pp. 47-53, 2017. Abstract | Links | BibTeX | Tags: @article{Zhou2017, title = {Chromatographic efficiency and selectivity in top-down proteomics of histones.}, author = {Y. Zhou and X. Zhang and L. Fornelli and P.D. Compton and N. Kelleher and M.J. Wirth}, url = {http://www.sciencedirect.com/science/article/pii/S1570023216310972?via%3Dihub}, doi = {10.1016/j.jchromb.2016.12.027}, year = {2017}, date = {2017-02-15}, journal = {J Chromatogr B Analyt Technol Biomed Life Sci}, pages = {47-53}, abstract = {Histones are involved in epigenetic control of a wide variety of cellular processes through their multiple post-translational modifications. Their strongly cationic nature makes them challenging to separate with reversed-phase liquid chromatography coupled to mass spectrometry (RPLC-MS), where trifluoroacetic acid is avoided due to adduct formation. Columns with higher resolution are needed. In this work, RPLC-MS is performed on a histone sample using difluoroacetic acid and a 20-min gradient. Columns with C18 surfaces are compared for two different types of particle morphologies: 1) fully porous particles of 5μm in diameter, 2) superficially porous particles of 3μm in diameter with a shell of 0.2μm. The resolution for the histone separation is better for the latter column, but only when the modifier is trifluoroacetic acid, which is used with UV absorbance detection. When difluoroacetic acid is used for LCMS, the peaks broaden enough to erase the advantage in efficiency for the superficially porous particles. The fully porous and superficially porous cases show similar performance in RPLC-MS, with slightly higher resolution for the fully porous particles. The expected advantage of the shorter diffusion distances for the superficially porous particles is shown to be outweighed by the lower selectivity of its bonded phase.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Histones are involved in epigenetic control of a wide variety of cellular processes through their multiple post-translational modifications. Their strongly cationic nature makes them challenging to separate with reversed-phase liquid chromatography coupled to mass spectrometry (RPLC-MS), where trifluoroacetic acid is avoided due to adduct formation. Columns with higher resolution are needed. In this work, RPLC-MS is performed on a histone sample using difluoroacetic acid and a 20-min gradient. Columns with C18 surfaces are compared for two different types of particle morphologies: 1) fully porous particles of 5μm in diameter, 2) superficially porous particles of 3μm in diameter with a shell of 0.2μm. The resolution for the histone separation is better for the latter column, but only when the modifier is trifluoroacetic acid, which is used with UV absorbance detection. When difluoroacetic acid is used for LCMS, the peaks broaden enough to erase the advantage in efficiency for the superficially porous particles. The fully porous and superficially porous cases show similar performance in RPLC-MS, with slightly higher resolution for the fully porous particles. The expected advantage of the shorter diffusion distances for the superficially porous particles is shown to be outweighed by the lower selectivity of its bonded phase. |
Anderson, L C; DeHart, C J; Kaiser, N K; Fellers, R T; Smith, D F; Greer, J B; LeDuc, R D; Blakney, G T; Thomas, P M; Kelleher, N L; Hendrickson, C L Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry Journal Article J Proteome Res, 16 (2), pp. 1087-1096, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). @article{RN469, title = {Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry}, author = { L. C. Anderson and C. J. DeHart and N. K. Kaiser and R. T. Fellers and D. F. Smith and J. B. Greer and R. D. LeDuc and G. T. Blakney and P. M. Thomas and N. L. Kelleher and C. L. Hendrickson}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27936753}, doi = {10.1021/acs.jproteome.6b00696}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Proteome Res}, volume = {16}, number = {2}, pages = {1087-1096}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Cleland, T P; DeHart, C J; Fellers, R T; VanNispen, A J; Greer, J B; LeDuc, R D; Parker, W R; Thomas, P M; Kelleher, N L; Brodbelt, J S High-Throughput Analysis of Intact Human Proteins Using UVPD and HCD on an Orbitrap Mass Spectrometer Journal Article J Proteome Res, 16 (5), pp. 2072-2079, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). @article{RN458, title = {High-Throughput Analysis of Intact Human Proteins Using UVPD and HCD on an Orbitrap Mass Spectrometer}, author = { T. P. Cleland and C. J. DeHart and R. T. Fellers and A. J. VanNispen and J. B. Greer and R. D. LeDuc and W. R. Parker and P. M. Thomas and N. L. Kelleher and J. S. Brodbelt}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28412815}, doi = {10.1021/acs.jproteome.7b00043}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Proteome Res}, volume = {16}, number = {5}, pages = {2072-2079}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Clevenger, K D; Bok, J W; Ye, R; Miley, G P; Verdan, M H; Velk, T; Chen, C; Yang, K; Robey, M T; Gao, P; Lamprecht, M; Thomas, P M; Islam, M N; Palmer, J M; Wu, C C; Keller, N P; Kelleher, N L A scalable platform to identify fungal secondary metabolites and their gene clusters Journal Article Nat Chem Biol, 2017, ISSN: 1552-4469 (Electronic) 1552-4450 (Linking). @article{RN456, title = {A scalable platform to identify fungal secondary metabolites and their gene clusters}, author = { K. D. Clevenger and J. W. Bok and R. Ye and G. P. Miley and M. H. Verdan and T. Velk and C. Chen and K. Yang and M. T. Robey and P. Gao and M. Lamprecht and P. M. Thomas and M. N. Islam and J. M. Palmer and C. C. Wu and N. P. Keller and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28604695}, doi = {10.1038/nchembio.2408}, issn = {1552-4469 (Electronic) 1552-4450 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {Nat Chem Biol}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Clevenger, K D; Mascarenhas, R; Catlin, D; Wu, R; Kelleher, N L; Drake, E J; Gulick, A M; Liu, D; Fast, W Substrate Trapping in the Siderophore Tailoring Enzyme PvdQ Journal Article ACS Chem Biol, 12 (3), pp. 643-647, 2017, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking). @article{RN464, title = {Substrate Trapping in the Siderophore Tailoring Enzyme PvdQ}, author = { K. D. Clevenger and R. Mascarenhas and D. Catlin and R. Wu and N. L. Kelleher and E. J. Drake and A. M. Gulick and D. Liu and W. Fast}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28186406}, doi = {10.1021/acschembio.7b00031}, issn = {1554-8937 (Electronic) 1554-8929 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {ACS Chem Biol}, volume = {12}, number = {3}, pages = {643-647}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
DeHart, C J; Fellers, R T; Fornelli, L; Kelleher, N L; Thomas, P M Bioinformatics Analysis of Top-Down Mass Spectrometry Data with ProSight Lite Journal Article Methods Mol Biol, 1558 , pp. 381-394, 2017, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). @article{RN466, title = {Bioinformatics Analysis of Top-Down Mass Spectrometry Data with ProSight Lite}, author = { C. J. DeHart and R. T. Fellers and L. Fornelli and N. L. Kelleher and P. M. Thomas}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28150248}, doi = {10.1007/978-1-4939-6783-4_18}, issn = {1940-6029 (Electronic) 1064-3745 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {Methods Mol Biol}, volume = {1558}, pages = {381-394}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Fornelli, L; Durbin, K R; Fellers, R T; Early, B P; Greer, J B; LeDuc, R D; Compton, P D; Kelleher, N L Advancing Top-down Analysis of the Human Proteome Using a Benchtop Quadrupole-Orbitrap Mass Spectrometer Journal Article J Proteome Res, 16 (2), pp. 609-618, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). @article{RN465, title = {Advancing Top-down Analysis of the Human Proteome Using a Benchtop Quadrupole-Orbitrap Mass Spectrometer}, author = { L. Fornelli and K. R. Durbin and R. T. Fellers and B. P. Early and J. B. Greer and R. D. LeDuc and P. D. Compton and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28152595}, doi = {10.1021/acs.jproteome.6b00698}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Proteome Res}, volume = {16}, number = {2}, pages = {609-618}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Fornelli, L; Toby, T K; Schachner, L F; Doubleday, P F; Srzentic, K; DeHart, C J; Kelleher, N L Top-down proteomics: Where we are, where we are going? Journal Article J Proteomics, 2017, ISSN: 1876-7737 (Electronic) 1874-3919 (Linking). @article{RN463, title = {Top-down proteomics: Where we are, where we are going?}, author = { L. Fornelli and T. K. Toby and L. F. Schachner and P. F. Doubleday and K. Srzentic and C. J. DeHart and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28188863}, doi = {10.1016/j.jprot.2017.02.002}, issn = {1876-7737 (Electronic) 1874-3919 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Proteomics}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Gan, R; Perez, J G; Carlson, E D; Ntai, I; Isaacs, F J; Kelleher, N L; Jewett, M C Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins Journal Article Biotechnol Bioeng, 114 (5), pp. 1074-1086, 2017, ISSN: 1097-0290 (Electronic) 0006-3592 (Linking). @article{RN468, title = {Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins}, author = { R. Gan and J. G. Perez and E. D. Carlson and I. Ntai and F. J. Isaacs and N. L. Kelleher and M. C. Jewett}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27987323}, doi = {10.1002/bit.26239}, issn = {1097-0290 (Electronic) 0006-3592 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {Biotechnol Bioeng}, volume = {114}, number = {5}, pages = {1074-1086}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Goering, A W; Li, J; McClure, R A; Thomson, R J; Jewett, M C; Kelleher, N L In Vitro Reconstruction of Nonribosomal Peptide Biosynthesis Directly from DNA Using Cell-Free Protein Synthesis Journal Article ACS Synth Biol, 6 (1), pp. 39-44, 2017, ISSN: 2161-5063 (Electronic) 2161-5063 (Linking). @article{RN475, title = {In Vitro Reconstruction of Nonribosomal Peptide Biosynthesis Directly from DNA Using Cell-Free Protein Synthesis}, author = { A. W. Goering and J. Li and R. A. McClure and R. J. Thomson and M. C. Jewett and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27478992}, doi = {10.1021/acssynbio.6b00160}, issn = {2161-5063 (Electronic) 2161-5063 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {ACS Synth Biol}, volume = {6}, number = {1}, pages = {39-44}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Greer, S M; Holden, D D; Fellers, R; Kelleher, N L; Brodbelt, J S Modulation of Protein Fragmentation Through Carbamylation of Primary Amines Journal Article J Am Soc Mass Spectrom, 28 (8), pp. 1587-1599, 2017, ISSN: 1879-1123 (Electronic) 1044-0305 (Linking). @article{RN459, title = {Modulation of Protein Fragmentation Through Carbamylation of Primary Amines}, author = { S. M. Greer and D. D. Holden and R. Fellers and N. L. Kelleher and J. S. Brodbelt}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28374316}, doi = {10.1007/s13361-017-1648-5}, issn = {1879-1123 (Electronic) 1044-0305 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Am Soc Mass Spectrom}, volume = {28}, number = {8}, pages = {1587-1599}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Haverland, N A; Skinner, O S; Fellers, R T; Tariq, A A; Early, B P; LeDuc, R D; Fornelli, L; Compton, P D; Kelleher, N L Defining Gas-Phase Fragmentation Propensities of Intact Proteins During Native Top-Down Mass Spectrometry Journal Article J Am Soc Mass Spectrom, 28 (6), pp. 1203-1215, 2017, ISSN: 1879-1123 (Electronic) 1044-0305 (Linking). @article{RN460, title = {Defining Gas-Phase Fragmentation Propensities of Intact Proteins During Native Top-Down Mass Spectrometry}, author = { N. A. Haverland and O. S. Skinner and R. T. Fellers and A. A. Tariq and B. P. Early and R. D. LeDuc and L. Fornelli and P. D. Compton and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28374312}, doi = {10.1007/s13361-017-1635-x}, issn = {1879-1123 (Electronic) 1044-0305 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Am Soc Mass Spectrom}, volume = {28}, number = {6}, pages = {1203-1215}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Mandacaru, S C; do Vale, L H; Vahidi, S; Xiao, Y; Skinner, O S; Ricart, C A; Kelleher, N L; de Sousa, M V; Konermann, L Characterizing the Structure and Oligomerization of Major Royal Jelly Protein 1 (MRJP1) by Mass Spectrometry and Complementary Biophysical Tools Journal Article Biochemistry, 56 (11), pp. 1645-1655, 2017, ISSN: 1520-4995 (Electronic) 0006-2960 (Linking). @article{RN462, title = {Characterizing the Structure and Oligomerization of Major Royal Jelly Protein 1 (MRJP1) by Mass Spectrometry and Complementary Biophysical Tools}, author = { S. C. Mandacaru and L. H. do Vale and S. Vahidi and Y. Xiao and O. S. Skinner and C. A. Ricart and N. L. Kelleher and M. V. de Sousa and L. Konermann}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28252287}, doi = {10.1021/acs.biochem.7b00020}, issn = {1520-4995 (Electronic) 0006-2960 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {Biochemistry}, volume = {56}, number = {11}, pages = {1645-1655}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Piunti, A; Hashizume, R; Morgan, M A; Bartom, E T; Horbinski, C M; Marshall, S A; Rendleman, E J; Ma, Q; Takahashi, Y H; Woodfin, A R; Misharin, A V; Abshiru, N A; Lulla, R R; Saratsis, A M; Kelleher, N L; James, C D; Shilatifard, A Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas Journal Article Nat Med, 23 (4), pp. 493-500, 2017, ISSN: 1546-170X (Electronic) 1078-8956 (Linking). @article{RN461, title = {Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas}, author = { A. Piunti and R. Hashizume and M. A. Morgan and E. T. Bartom and C. M. Horbinski and S. A. Marshall and E. J. Rendleman and Q. Ma and Y. H. Takahashi and A. R. Woodfin and A. V. Misharin and N. A. Abshiru and R. R. Lulla and A. M. Saratsis and N. L. Kelleher and C. D. James and A. Shilatifard}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28263307}, doi = {10.1038/nm.4296}, issn = {1546-170X (Electronic) 1078-8956 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {Nat Med}, volume = {23}, number = {4}, pages = {493-500}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Schroeter, E R; DeHart, C J; Cleland, T P; Zheng, W; Thomas, P M; Kelleher, N L; Bern, M; Schweitzer, M H Expansion for the Brachylophosaurus canadensis Collagen I Sequence and Additional Evidence of the Preservation of Cretaceous Protein Journal Article J Proteome Res, 16 (2), pp. 920-932, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). @article{RN467, title = {Expansion for the Brachylophosaurus canadensis Collagen I Sequence and Additional Evidence of the Preservation of Cretaceous Protein}, author = { E. R. Schroeter and C. J. DeHart and T. P. Cleland and W. Zheng and P. M. Thomas and N. L. Kelleher and M. Bern and M. H. Schweitzer}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28111950}, doi = {10.1021/acs.jproteome.6b00873}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {J Proteome Res}, volume = {16}, number = {2}, pages = {920-932}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Toby, T K; Abecassis, M M; Kim, K; Thomas, P M; Fellers, R T; LeDuc, R D; Kelleher, N L; Demetris, J; Levitsky, J Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients Journal Article Am J Transplant, 2017, ISSN: 1600-6143 (Electronic) 1600-6135 (Linking). @article{RN457, title = {Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients}, author = { T. K. Toby and M. M. Abecassis and K. Kim and P. M. Thomas and R. T. Fellers and R. D. LeDuc and N. L. Kelleher and J. Demetris and J. Levitsky}, url = {http://www.ncbi.nlm.nih.gov/pubmed/28510335}, doi = {10.1111/ajt.14359}, issn = {1600-6143 (Electronic) 1600-6135 (Linking)}, year = {2017}, date = {2017-01-01}, journal = {Am J Transplant}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2016 |
Chen, Y; McClure, R A; Kelleher, N L Screening for Expressed Nonribosomal Peptide Synthetases and Polyketide Synthases Using LC-MS/MS-Based Proteomics Journal Article Methods Mol Biol, 1401 , pp. 135-47, 2016, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). @article{RN490, title = {Screening for Expressed Nonribosomal Peptide Synthetases and Polyketide Synthases Using LC-MS/MS-Based Proteomics}, author = { Y. Chen and R. A. McClure and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26831706}, doi = {10.1007/978-1-4939-3375-4_9}, issn = {1940-6029 (Electronic) 1064-3745 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Methods Mol Biol}, volume = {1401}, pages = {135-47}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Durbin, K R; Fornelli, L; Fellers, R T; Doubleday, P F; Narita, M; Kelleher, N L Quantitation and Identification of Thousands of Human Proteoforms below 30 kDa Journal Article J Proteome Res, 15 (3), pp. 976-82, 2016, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). @article{RN491, title = {Quantitation and Identification of Thousands of Human Proteoforms below 30 kDa}, author = { K. R. Durbin and L. Fornelli and R. T. Fellers and P. F. Doubleday and M. Narita and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26795204}, doi = {10.1021/acs.jproteome.5b00997}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {J Proteome Res}, volume = {15}, number = {3}, pages = {976-82}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Goering, A W; McClure, R A; Doroghazi, J R; Albright, J C; Haverland, N A; Zhang, Y; Ju, K S; Thomson, R J; Metcalf, W W; Kelleher, N L ACS Cent Sci, 2 (2), pp. 99-108, 2016, ISSN: 2374-7943 (Print) 2374-7943 (Linking). @article{RN483, title = {Metabologenomics: Correlation of Microbial Gene Clusters with Metabolites Drives Discovery of a Nonribosomal Peptide with an Unusual Amino Acid Monomer}, author = { A. W. Goering and R. A. McClure and J. R. Doroghazi and J. C. Albright and N. A. Haverland and Y. Zhang and K. S. Ju and R. J. Thomson and W. W. Metcalf and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27163034}, doi = {10.1021/acscentsci.5b00331}, issn = {2374-7943 (Print) 2374-7943 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {ACS Cent Sci}, volume = {2}, number = {2}, pages = {99-108}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Gunn, B; Schneider, J; Shansab, M; Bastian, A R; Fahrbach, K; th Smith, A; Mahan, A; Karim, M; Licht, A; Zvonar, I; Tedesco, J; Anderson, M; Chapel, A; Suscovich, T; Malaspina, D; Streeck, H; Walker, B D; Kim, A; Lauer, G; Altfeld, M; Pillai, S; Szleifer, I; Kelleher, N L; Kiser, P F; Hope, T J; Alter, G Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16 Journal Article Mucosal Immunol, 9 (6), pp. 1549-1558, 2016, ISSN: 1935-3456 (Electronic) 1933-0219 (Linking). @article{RN486, title = {Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16}, author = { B. Gunn and J. Schneider and M. Shansab and A. R. Bastian and K. Fahrbach and A. th Smith and A. Mahan and M. Karim and A. Licht and I. Zvonar and J. Tedesco and M. Anderson and A. Chapel and T. Suscovich and D. Malaspina and H. Streeck and B. D. Walker and A. Kim and G. Lauer and M. Altfeld and S. Pillai and I. Szleifer and N. L. Kelleher and P. F. Kiser and T. J. Hope and G. Alter}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26960182}, doi = {10.1038/mi.2016.8}, issn = {1935-3456 (Electronic) 1933-0219 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Mucosal Immunol}, volume = {9}, number = {6}, pages = {1549-1558}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Hattori, T; Lai, D; Dementieva, I S; Montano, S P; Kurosawa, K; Zheng, Y; Akin, L R; Swist-Rosowska, K M; Grzybowski, A T; Koide, A; Krajewski, K; Strahl, B D; Kelleher, N L; Ruthenburg, A J; Koide, S Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation Journal Article Proc Natl Acad Sci U S A, 113 (8), pp. 2092-7, 2016, ISSN: 1091-6490 (Electronic) 0027-8424 (Linking). @article{RN489, title = {Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation}, author = { T. Hattori and D. Lai and I. S. Dementieva and S. P. Montano and K. Kurosawa and Y. Zheng and L. R. Akin and K. M. Swist-Rosowska and A. T. Grzybowski and A. Koide and K. Krajewski and B. D. Strahl and N. L. Kelleher and A. J. Ruthenburg and S. Koide}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26862167}, doi = {10.1073/pnas.1522691113}, issn = {1091-6490 (Electronic) 0027-8424 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, number = {8}, pages = {2092-7}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Henke, M T; Kelleher, N L Modern mass spectrometry for synthetic biology and structure-based discovery of natural products Journal Article Nat Prod Rep, 33 (8), pp. 942-50, 2016, ISSN: 1460-4752 (Electronic) 0265-0568 (Linking). @article{RN477, title = {Modern mass spectrometry for synthetic biology and structure-based discovery of natural products}, author = { M. T. Henke and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27376415}, doi = {10.1039/c6np00024j}, issn = {1460-4752 (Electronic) 0265-0568 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Nat Prod Rep}, volume = {33}, number = {8}, pages = {942-50}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Henke, M T; Soukup, A A; Goering, A W; McClure, R A; Thomson, R J; Keller, N P; Kelleher, N L New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans Journal Article ACS Chem Biol, 11 (8), pp. 2117-23, 2016, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking). @article{RN479, title = {New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans}, author = { M. T. Henke and A. A. Soukup and A. W. Goering and R. A. McClure and R. J. Thomson and N. P. Keller and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27310134}, doi = {10.1021/acschembio.6b00398}, issn = {1554-8937 (Electronic) 1554-8929 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {ACS Chem Biol}, volume = {11}, number = {8}, pages = {2117-23}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Kenney, G E; Goering, A W; Ross, M O; DeHart, C J; Thomas, P M; Hoffman, B M; Kelleher, N L; Rosenzweig, A C Characterization of Methanobactin from Methylosinus sp. LW4 Journal Article J Am Chem Soc, 138 (35), pp. 11124-7, 2016, ISSN: 1520-5126 (Electronic) 0002-7863 (Linking). @article{RN474, title = {Characterization of Methanobactin from Methylosinus sp. LW4}, author = { G. E. Kenney and A. W. Goering and M. O. Ross and C. J. DeHart and P. M. Thomas and B. M. Hoffman and N. L. Kelleher and A. C. Rosenzweig}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27527063}, doi = {10.1021/jacs.6b06821}, issn = {1520-5126 (Electronic) 0002-7863 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {J Am Chem Soc}, volume = {138}, number = {35}, pages = {11124-7}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
LaFave, L M; Beguelin, W; Koche, R; Teater, M; Spitzer, B; Chramiec, A; Papalexi, E; Keller, M D; Hricik, T; Konstantinoff, K; Micol, J B; Durham, B; Knutson, S K; Campbell, J E; Blum, G; Shi, X; Doud, E H; Krivtsov, A V; Chung, Y R; Khodos, I; de Stanchina, E; Ouerfelli, O; Adusumilli, P S; Thomas, P M; Kelleher, N L; Luo, M; Keilhack, H; Abdel-Wahab, O; Melnick, A; Armstrong, S A; Levine, R L Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status" Journal Article Nat Med, 22 (6), pp. 578-9, 2016, ISSN: 1546-170X (Electronic) 1078-8956 (Linking). @article{RN481, title = {Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status"}, author = { L. M. LaFave and W. Beguelin and R. Koche and M. Teater and B. Spitzer and A. Chramiec and E. Papalexi and M. D. Keller and T. Hricik and K. Konstantinoff and J. B. Micol and B. Durham and S. K. Knutson and J. E. Campbell and G. Blum and X. Shi and E. H. Doud and A. V. Krivtsov and Y. R. Chung and I. Khodos and E. de Stanchina and O. Ouerfelli and P. S. Adusumilli and P. M. Thomas and N. L. Kelleher and M. Luo and H. Keilhack and O. Abdel-Wahab and A. Melnick and S. A. Armstrong and R. L. Levine}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27270773}, doi = {10.1038/nm.4094}, issn = {1546-170X (Electronic) 1078-8956 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Nat Med}, volume = {22}, number = {6}, pages = {578-9}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Liu, F; Koval, M; Ranganathan, S; Fanayan, S; Hancock, W S; Lundberg, E K; Beavis, R C; Lane, L; Duek, P; McQuade, L; Kelleher, N L; Baker, M S Systems Proteomics View of the Endogenous Human Claudin Protein Family Journal Article J Proteome Res, 15 (2), pp. 339-59, 2016, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). @article{RN495, title = {Systems Proteomics View of the Endogenous Human Claudin Protein Family}, author = { F. Liu and M. Koval and S. Ranganathan and S. Fanayan and W. S. Hancock and E. K. Lundberg and R. C. Beavis and L. Lane and P. Duek and L. McQuade and N. L. Kelleher and M. S. Baker}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26680015}, doi = {10.1021/acs.jproteome.5b00769}, issn = {1535-3907 (Electronic) 1535-3893 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {J Proteome Res}, volume = {15}, number = {2}, pages = {339-59}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
McClure, R A; Goering, A W; Ju, K S; Baccile, J A; Schroeder, F C; Metcalf, W W; Thomson, R J; Kelleher, N L Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations Journal Article ACS Chem Biol, 11 (12), pp. 3452-3460, 2016, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking). @article{RN472, title = {Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations}, author = { R. A. McClure and A. W. Goering and K. S. Ju and J. A. Baccile and F. C. Schroeder and W. W. Metcalf and R. J. Thomson and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27809474}, doi = {10.1021/acschembio.6b00779}, issn = {1554-8937 (Electronic) 1554-8929 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {ACS Chem Biol}, volume = {11}, number = {12}, pages = {3452-3460}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Melani, R D; Seckler, H S; Skinner, O S; Vale, Do L H; Catherman, A D; Havugimana, P C; de Sousa, Valle M; Domont, G B; Kelleher, N L; Compton, P D CN-GELFrEE - Clear Native Gel-eluted Liquid Fraction Entrapment Electrophoresis Journal Article J Vis Exp, (108), pp. 53597, 2016, ISSN: 1940-087X (Electronic) 1940-087X (Linking). @article{RN485, title = {CN-GELFrEE - Clear Native Gel-eluted Liquid Fraction Entrapment Electrophoresis}, author = { R. D. Melani and H. S. Seckler and O. S. Skinner and L. H. Do Vale and A. D. Catherman and P. C. Havugimana and M. Valle de Sousa and G. B. Domont and N. L. Kelleher and P. D. Compton}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26967310}, doi = {10.3791/53597}, issn = {1940-087X (Electronic) 1940-087X (Linking)}, year = {2016}, date = {2016-01-01}, journal = {J Vis Exp}, number = {108}, pages = {53597}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Melani, R D; Skinner, O S; Fornelli, L; Domont, G B; Compton, P D; Kelleher, N L Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics Journal Article Mol Cell Proteomics, 15 (7), pp. 2423-34, 2016, ISSN: 1535-9484 (Electronic) 1535-9476 (Linking). @article{RN482, title = {Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics}, author = { R. D. Melani and O. S. Skinner and L. Fornelli and G. B. Domont and P. D. Compton and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27178327}, doi = {10.1074/mcp.M115.056523}, issn = {1535-9484 (Electronic) 1535-9476 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Mol Cell Proteomics}, volume = {15}, number = {7}, pages = {2423-34}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Moussazadeh, N; Berman, S H; Laufer, I; Gounder, M; Zheng, Y; Sommer, J; Bilsky, M H; Kelleher, N L; Brennan, C 365 Epigenetic Profiling Reveals a Unique Histone Code in Chordoma Journal Article Neurosurgery, 63 Suppl 1 , pp. 208, 2016, ISSN: 1524-4040 (Electronic) 0148-396X (Linking). @article{RN476, title = {365 Epigenetic Profiling Reveals a Unique Histone Code in Chordoma}, author = { N. Moussazadeh and S. H. Berman and I. Laufer and M. Gounder and Y. Zheng and J. Sommer and M. H. Bilsky and N. L. Kelleher and C. Brennan}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27399562}, doi = {10.1227/01.neu.0000489853.78064.b2}, issn = {1524-4040 (Electronic) 0148-396X (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Neurosurgery}, volume = {63 Suppl 1}, pages = {208}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Ntai, I; LeDuc, R D; Fellers, R T; Erdmann-Gilmore, P; Davies, S R; Rumsey, J; Early, B P; Thomas, P M; Li, S; Compton, P D; Ellis, M J; Ruggles, K V; Fenyo, D; Boja, E S; Rodriguez, H; Townsend, R R; Kelleher, N L Integrated Bottom-Up and Top-Down Proteomics of Patient-Derived Breast Tumor Xenografts Journal Article Mol Cell Proteomics, 15 (1), pp. 45-56, 2016, ISSN: 1535-9484 (Electronic) 1535-9476 (Linking). @article{RN498, title = {Integrated Bottom-Up and Top-Down Proteomics of Patient-Derived Breast Tumor Xenografts}, author = { I. Ntai and R. D. LeDuc and R. T. Fellers and P. Erdmann-Gilmore and S. R. Davies and J. Rumsey and B. P. Early and P. M. Thomas and S. Li and P. D. Compton and M. J. Ellis and K. V. Ruggles and D. Fenyo and E. S. Boja and H. Rodriguez and R. R. Townsend and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26503891}, doi = {10.1074/mcp.M114.047480}, issn = {1535-9484 (Electronic) 1535-9476 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Mol Cell Proteomics}, volume = {15}, number = {1}, pages = {45-56}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Ntai, I; Toby, T K; LeDuc, R D; Kelleher, N L A Method for Label-Free, Differential Top-Down Proteomics Journal Article Methods Mol Biol, 1410 , pp. 121-33, 2016, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). @article{RN488, title = {A Method for Label-Free, Differential Top-Down Proteomics}, author = { I. Ntai and T. K. Toby and R. D. LeDuc and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26867742}, doi = {10.1007/978-1-4939-3524-6_8}, issn = {1940-6029 (Electronic) 1064-3745 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Methods Mol Biol}, volume = {1410}, pages = {121-33}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Ong, T H; Romanova, E V; Roberts-Galbraith, R H; Yang, N; Zimmerman, T A; Collins, 3rd J J; Lee, J E; Kelleher, N L; Newmark, P A; Sweedler, J V Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea Journal Article J Biol Chem, 291 (15), pp. 8109-20, 2016, ISSN: 1083-351X (Electronic) 0021-9258 (Linking). @article{RN487, title = {Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea}, author = { T. H. Ong and E. V. Romanova and R. H. Roberts-Galbraith and N. Yang and T. A. Zimmerman and J. J. 3rd Collins and J. E. Lee and N. L. Kelleher and P. A. Newmark and J. V. Sweedler}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26884331}, doi = {10.1074/jbc.M115.709196}, issn = {1083-351X (Electronic) 0021-9258 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {J Biol Chem}, volume = {291}, number = {15}, pages = {8109-20}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Savaryn, J P; Skinner, O S; Fornelli, L; Fellers, R T; Compton, P D; Terhune, S S; Abecassis, M M; Kelleher, N L Targeted analysis of recombinant NF kappa B (RelA/p65) by denaturing and native top down mass spectrometry Journal Article J Proteomics, 134 , pp. 76-84, 2016, ISSN: 1876-7737 (Electronic) 1874-3919 (Linking). @article{RN505, title = {Targeted analysis of recombinant NF kappa B (RelA/p65) by denaturing and native top down mass spectrometry}, author = { J. P. Savaryn and O. S. Skinner and L. Fornelli and R. T. Fellers and P. D. Compton and S. S. Terhune and M. M. Abecassis and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/25952688}, doi = {10.1016/j.jprot.2015.04.025}, issn = {1876-7737 (Electronic) 1874-3919 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {J Proteomics}, volume = {134}, pages = {76-84}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Savaryn, J P; Toby, T K; Catherman, A D; Fellers, R T; LeDuc, R D; Thomas, P M; Friedewald, J J; Salomon, D R; Abecassis, M M; Kelleher, N L Proteomics, 16 (14), pp. 2048-58, 2016, ISSN: 1615-9861 (Electronic) 1615-9853 (Linking). @article{RN484, title = {Comparative top down proteomics of peripheral blood mononuclear cells from kidney transplant recipients with normal kidney biopsies or acute rejection}, author = { J. P. Savaryn and T. K. Toby and A. D. Catherman and R. T. Fellers and R. D. LeDuc and P. M. Thomas and J. J. Friedewald and D. R. Salomon and M. M. Abecassis and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27120713}, doi = {10.1002/pmic.201600008}, issn = {1615-9861 (Electronic) 1615-9853 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Proteomics}, volume = {16}, number = {14}, pages = {2048-58}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Savaryn, J P; Toby, T K; Kelleher, N L A researcher's guide to mass spectrometry-based proteomics Journal Article Proteomics, 16 (18), pp. 2435-43, 2016, ISSN: 1615-9861 (Electronic) 1615-9853 (Linking). @article{RN473, title = {A researcher's guide to mass spectrometry-based proteomics}, author = { J. P. Savaryn and T. K. Toby and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27553853}, doi = {10.1002/pmic.201600113}, issn = {1615-9861 (Electronic) 1615-9853 (Linking)}, year = {2016}, date = {2016-01-01}, journal = {Proteomics}, volume = {16}, number = {18}, pages = {2435-43}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Schroeter, E R; DeHart, C J; Schweitzer, M H; Thomas, P M; Kelleher, N L PeerJ, 4 , pp. e2603, 2016, ISSN: 2167-8359 (Print). @article{RN471, title = {Bone protein "extractomics": comparing the efficiency of bone protein extractions of Gallus gallus in tandem mass spectrometry, with an eye towards paleoproteomics}, author = { E. R. Schroeter and C. J. DeHart and M. H. Schweitzer and P. M. Thomas and N. L. Kelleher}, url = {http://www.ncbi.nlm.nih.gov/pubmed/27812413}, doi = {10.7717/peerj.2603}, issn = {2167-8359 (Print)}, year = {2016}, date = {2016-01-01}, journal = {PeerJ}, volume = {4}, pages = {e2603}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2017 |
The Mechanism of N2 Reduction Catalyzed by Fe-Nitrogenase Involves Reductive Elimination of H2 Journal Article Biochemistry, 2017. |
Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability. Journal Article Nat. Genet., 49 (11), pp. 1647-1653, 2017. |
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence. Journal Article Nat. Genet., 2017. |
Top-down characterization of endogenous protein complexes with native proteomics. Journal Article Nat. Chem. Biol., 2017. |
Biochemistry, 56 (43), pp. 5844-5845, 2017. |
Native Electron Capture Dissociation Maps to Iron-Binding Channels in Horse Spleen Ferritin Journal Article Anal. Chem. , 89 (20), pp. 10711-10716, 2017. |
Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes Journal Article Proteomics, 17 (19), 2017. |
UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition Journal Article Cell. Rep. , 21 (3), pp. 628-640, 2017. |
Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring. Journal Article Nat Chem Biol, 13 (10), pp. 1063-1065, 2017. |
A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation. Journal Article Genes. Dev., 19 , pp. 2003-2014, 2017. |
A synthetic biology approach to probing nucleosome symmetry Journal Article eLife, (6), 2017. |
Biochemistry, 56 (37), pp. 4951-4961, 2017. |
Diversity of Amyloid-beta Proteoforms in the Alzheimer’s Disease Brain Journal Article Sci. Rep. , 7 (1), pp. 9520, 2017. |
Chromatographic efficiency and selectivity in top-down proteomics of histones. Journal Article J Chromatogr B Analyt Technol Biomed Life Sci, pp. 47-53, 2017. |
Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry Journal Article J Proteome Res, 16 (2), pp. 1087-1096, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). |
High-Throughput Analysis of Intact Human Proteins Using UVPD and HCD on an Orbitrap Mass Spectrometer Journal Article J Proteome Res, 16 (5), pp. 2072-2079, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). |
A scalable platform to identify fungal secondary metabolites and their gene clusters Journal Article Nat Chem Biol, 2017, ISSN: 1552-4469 (Electronic) 1552-4450 (Linking). |
Substrate Trapping in the Siderophore Tailoring Enzyme PvdQ Journal Article ACS Chem Biol, 12 (3), pp. 643-647, 2017, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking). |
Bioinformatics Analysis of Top-Down Mass Spectrometry Data with ProSight Lite Journal Article Methods Mol Biol, 1558 , pp. 381-394, 2017, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). |
Advancing Top-down Analysis of the Human Proteome Using a Benchtop Quadrupole-Orbitrap Mass Spectrometer Journal Article J Proteome Res, 16 (2), pp. 609-618, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). |
Top-down proteomics: Where we are, where we are going? Journal Article J Proteomics, 2017, ISSN: 1876-7737 (Electronic) 1874-3919 (Linking). |
Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins Journal Article Biotechnol Bioeng, 114 (5), pp. 1074-1086, 2017, ISSN: 1097-0290 (Electronic) 0006-3592 (Linking). |
In Vitro Reconstruction of Nonribosomal Peptide Biosynthesis Directly from DNA Using Cell-Free Protein Synthesis Journal Article ACS Synth Biol, 6 (1), pp. 39-44, 2017, ISSN: 2161-5063 (Electronic) 2161-5063 (Linking). |
Modulation of Protein Fragmentation Through Carbamylation of Primary Amines Journal Article J Am Soc Mass Spectrom, 28 (8), pp. 1587-1599, 2017, ISSN: 1879-1123 (Electronic) 1044-0305 (Linking). |
Defining Gas-Phase Fragmentation Propensities of Intact Proteins During Native Top-Down Mass Spectrometry Journal Article J Am Soc Mass Spectrom, 28 (6), pp. 1203-1215, 2017, ISSN: 1879-1123 (Electronic) 1044-0305 (Linking). |
Characterizing the Structure and Oligomerization of Major Royal Jelly Protein 1 (MRJP1) by Mass Spectrometry and Complementary Biophysical Tools Journal Article Biochemistry, 56 (11), pp. 1645-1655, 2017, ISSN: 1520-4995 (Electronic) 0006-2960 (Linking). |
Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas Journal Article Nat Med, 23 (4), pp. 493-500, 2017, ISSN: 1546-170X (Electronic) 1078-8956 (Linking). |
Expansion for the Brachylophosaurus canadensis Collagen I Sequence and Additional Evidence of the Preservation of Cretaceous Protein Journal Article J Proteome Res, 16 (2), pp. 920-932, 2017, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). |
Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients Journal Article Am J Transplant, 2017, ISSN: 1600-6143 (Electronic) 1600-6135 (Linking). |
2016 |
Screening for Expressed Nonribosomal Peptide Synthetases and Polyketide Synthases Using LC-MS/MS-Based Proteomics Journal Article Methods Mol Biol, 1401 , pp. 135-47, 2016, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). |
Quantitation and Identification of Thousands of Human Proteoforms below 30 kDa Journal Article J Proteome Res, 15 (3), pp. 976-82, 2016, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). |
ACS Cent Sci, 2 (2), pp. 99-108, 2016, ISSN: 2374-7943 (Print) 2374-7943 (Linking). |
Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16 Journal Article Mucosal Immunol, 9 (6), pp. 1549-1558, 2016, ISSN: 1935-3456 (Electronic) 1933-0219 (Linking). |
Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation Journal Article Proc Natl Acad Sci U S A, 113 (8), pp. 2092-7, 2016, ISSN: 1091-6490 (Electronic) 0027-8424 (Linking). |
Modern mass spectrometry for synthetic biology and structure-based discovery of natural products Journal Article Nat Prod Rep, 33 (8), pp. 942-50, 2016, ISSN: 1460-4752 (Electronic) 0265-0568 (Linking). |
New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans Journal Article ACS Chem Biol, 11 (8), pp. 2117-23, 2016, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking). |
Characterization of Methanobactin from Methylosinus sp. LW4 Journal Article J Am Chem Soc, 138 (35), pp. 11124-7, 2016, ISSN: 1520-5126 (Electronic) 0002-7863 (Linking). |
Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status" Journal Article Nat Med, 22 (6), pp. 578-9, 2016, ISSN: 1546-170X (Electronic) 1078-8956 (Linking). |
Systems Proteomics View of the Endogenous Human Claudin Protein Family Journal Article J Proteome Res, 15 (2), pp. 339-59, 2016, ISSN: 1535-3907 (Electronic) 1535-3893 (Linking). |
Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations Journal Article ACS Chem Biol, 11 (12), pp. 3452-3460, 2016, ISSN: 1554-8937 (Electronic) 1554-8929 (Linking). |
CN-GELFrEE - Clear Native Gel-eluted Liquid Fraction Entrapment Electrophoresis Journal Article J Vis Exp, (108), pp. 53597, 2016, ISSN: 1940-087X (Electronic) 1940-087X (Linking). |
Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics Journal Article Mol Cell Proteomics, 15 (7), pp. 2423-34, 2016, ISSN: 1535-9484 (Electronic) 1535-9476 (Linking). |
365 Epigenetic Profiling Reveals a Unique Histone Code in Chordoma Journal Article Neurosurgery, 63 Suppl 1 , pp. 208, 2016, ISSN: 1524-4040 (Electronic) 0148-396X (Linking). |
Integrated Bottom-Up and Top-Down Proteomics of Patient-Derived Breast Tumor Xenografts Journal Article Mol Cell Proteomics, 15 (1), pp. 45-56, 2016, ISSN: 1535-9484 (Electronic) 1535-9476 (Linking). |
A Method for Label-Free, Differential Top-Down Proteomics Journal Article Methods Mol Biol, 1410 , pp. 121-33, 2016, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). |
Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea Journal Article J Biol Chem, 291 (15), pp. 8109-20, 2016, ISSN: 1083-351X (Electronic) 0021-9258 (Linking). |
Targeted analysis of recombinant NF kappa B (RelA/p65) by denaturing and native top down mass spectrometry Journal Article J Proteomics, 134 , pp. 76-84, 2016, ISSN: 1876-7737 (Electronic) 1874-3919 (Linking). |
Proteomics, 16 (14), pp. 2048-58, 2016, ISSN: 1615-9861 (Electronic) 1615-9853 (Linking). |
A researcher's guide to mass spectrometry-based proteomics Journal Article Proteomics, 16 (18), pp. 2435-43, 2016, ISSN: 1615-9861 (Electronic) 1615-9853 (Linking). |
PeerJ, 4 , pp. e2603, 2016, ISSN: 2167-8359 (Print). |