个人简介

Degrees 1997 Post-doctoral X-ray Crystallography IMB, University of Oregon 1989 PhD Chemistry University of California, Berkeley 1982 BA Chemistry State University of New York, Purchase Awards 2006, "Teacher of the Year", Biochemistry and Molecular Biology Graduate Group

研究领域

Structural Biochemistry, Enzymology and Protein Engineering of Protein-nucleic acid Interactions X-ray crystallography, protein and DNA structure and function, and protein engineering, focusing on enzymology and molecular recognition. Model systems include DNA and nucleotide binding proteins and enzymes.

Structural Biochemistry, Enzymology and Protein Engineering of Protein-nucleic acid Interactions. My lab uses X-ray crystallography, biochemistry and molecular genetics to dissect and engineer mechanisms of enzymes involved in nucleic acid metabolism. A primary focus is on the mechanism and regulation of Cytidine Triphosphate Synthetase, the ultimate enzyme for pyrimidine biosynthesis, and a target for anti-cancer and anti-parasitic drugs. CTP Synthetases from all kingdoms form micron-scale intracellular filaments when inhibited by CTP product. We are particularly interested filament responses to metabolites, small-molecule ligands, and post-translational modifications and upstream and downstream interactors. A second interest in the lab is the structural basis for sequence-specific DNA binding proteins. Presently, we are how TALE proteins are able to recognize a variety of target DNA sequences with high affinity. We are investigating how the repetitive structure of the TALE DNA binding domains influences the relationship between length, affinity and sequence composition. Research Contribution Through the understanding of protein function at the atomic level, we can better target therapeutic strategies for proteins of medical interest by 1) re-engineering function; 2) focused efforts for developing small molecule ligand modulators, and 3) ascertaining their structural and functional relationships to other macromolecules. Research Interests Structural Biochemistry, Enzymology and Protein Engineering of Protein-nucleic acid Interactions X-ray crystallography, protein and DNA structure and function, and protein engineering, focusing on enzymology and molecular recognition. Model systems include DNA and nucleotide binding proteins and enzymes. RESEARCH TARGETS: 1) Mechanism and regulation of Cytidine Triphosphate Synthetase, the ultimate enzyme for pyrimidine biosynthesis, and a target for anti-cancer and anti-parasitic drugs. 2) DNA specificity and function of sequence-progammable TALE DNA binding proteins.

近期论文

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Habrian, C, Chandrasekhara, A, Shahrvini, B, Hua, BH, Lee, J, Jessinghaus, R, Barry, R, Gitai, Z, Kollman, J, and Baldwin, EP. 2016. Inhibition of E. coli CTP synthetase by NADH and other nicotinamides, and their mutual interactions with CTP and GTP. Biochemistry 55, 5554-65. Barry RM, Bitbol A-F, Lorestani A, Charles EJ, Habrian CH, Hansen JM, Li H-J, Baldwin EP, Wingreen NS, Kollman JM, and Gitai Z. 2014. Large-scale filament formation inhibits the activity of CTP synthetase. eLIFE 3, e03638. Ozes, A, Feoktistova, K, Avanzino, B, Baldwin, E and Fraser C. 2014. Real-time fluorescence assays to monitor duplex unwinding and ATPase activities of helicase proteins. Nature Protocols 9, 1645-61. Meckler JF, Bhakta MS, Kim M-S, Ovadia R, Habrian CH, Zykovich A, Yu A, Lockwood SH, Morbitzer R, Elsäesser J, Lahaye T, Segal DJ, and Baldwin EP. 2013. Quantitative Analysis of TALE-DNA Interactions Suggests Polarity Effects. Nucleic Acids Res. 41, 4118-28. Gaidenko, TA, Bei, X, Baldwin, EP and Price, CW. 2012. Two Surfaces of a Conserved Interdomain Linker Differentially Affect Output from the RST Sensing Module of the Bacillus subtilis Stressosome. J. Bacteriology 194, 3913-3921. Gaidenko TA, Bei X, Baldwin EP and Price CW. 2011. Substitutions in the Presumed Sensing Domain of the Bacillus subtilis Stressosome Affect Its Basal Output But Not Response to Environmental Signals. J. Bacteriology 193, 3558-3597. Gelato, K.A, Martin, S.S, Liu, P.H., Saunders, A.A., and E.P. Baldwin. 2008. Spatially-Directed Assembly of a Heterotetrameric Cre-Lox Synpase Restricts Recombination Specificity. J. Mol Biol. 385, 653-665. Chang, Y.F., Martin, S.S., Baldwin, E.P., & Carman, G.M. 2007. Phosphorylation of Human CTP Synthetase 1 by Protein Kinase C: Identification of Ser462 and Thr455 as major sites of phosphorylation. J. Biol. Chem. 282, 17613-22. Gelato, K.A., Martin, S.S., Wong, S., and Baldwin, E.P. 2006. Mulitple Levels of Affinity-Dependent DNA Discrimination in Cre-LoxP Recombination. Biochemistry 45, 12216-26. Gelato, K.A., Martin, S.S., Baldwin, E.P. 2005. Reversed DNA Strand Cleavage Specificity in Initiation of Cre-LoxP Recombination Induced by the His289Ala Active Site Substitution. J. Mol. Biol. 354, 233-45. Endrizzi, J.A., Kim, H., Anderson, P.M., Baldwin, E.P. 2005. Mechanisms of product feedback regulation and drug resistance in cytidine triphosphate synthetases from the structure of a CTP-inhibited complex. Biochemistry 44, 13491-9. Han, G.-S. , Sreenivas, A., Choi, M.-G. , Chang, Y.-F., Martin, S.S. , Baldwin, E.P., and G. M. Carman. 2005. Expression of Human CTP Synthetase in Saccharomyces cerevisiae Reveals Phosphorylation by Protein Kinase A, J. Biol. Chem. 280, 38328-36. Endrizzi, J.A., Kim, H., Anderson, P.M., Baldwin, E.P. 2004. Crystal Structure of Escherichia coli Cytidine Triphosphate Synthetase, a Nucleotide-Regulated Glutamine Amidotransferase/ATP-Dependent Amidoligase Fusion Protein and Homologue of Anticancer and Antiparasitic Drug Targets. Biochemistry 43, 6447-63. Friddle, RW, Klare, JE, Martin, SS, Corzett, M, Balhorn, R, Baldwin, EP, Baskin, RJ, and A Noy. 2004. Mechanism of DNA compaction by yeast mitochondria protein ABF2p. Biophysical J. 86, 1632-9. Baldwin EP, Martin SS, Abel J, Gelato KA, Kim H, Schultz PG, and SS Santoro. 2003. A specificity switch in selected Cre recombinase variants is mediated by macromolecular plasticity and water. Chem. Biol. 110, 1085-93. Martin SS, Wachi S, and EP Baldwin. 2003. Vanadate-based transition-state analog inhibitors of Cre-LoxP recombination. Biochem. Biophys Res. Comm. 308: 529-34. Brewer, LR, Friddle, R, Noy, A, Baldwin, E, Martin, SS, Corzett, M, Balhorn, R and RJ Baskin. 2003. Packaging of Single DNA Molecules by the Yeast Mitochondrial Protein ABF2p. Biophysical J. 85, 2519-24. Martin SS, Chu VC, and EP Baldwin. 2003. Modulation of active complex assembly and turnover rate by protein-DN Interactions in Cre-LoxP recombination. Biochemistry 42: 6814-6826. Martin SS, Pulido E, Chu, VC, Lechner TS, and EP Baldwin. 2002. The order of strand exchanges in Cre-LoxP recombination and its basis suggested by the crystal structure of a Cre-LoxP Holliday junction complex. J. Mol. Biol. 319: 107-127. Denison, MS, Pandini, A, Nagy, SR, Baldwin, EP, and Bonati, L. 2002. Ligand binding and activation of the Ah receptor. Chem. Biol. Interact. 141: 3-24. Woods KC, Martin SS, Chu VC and EP Baldwin. 2001. Quasi-equivalence in site-specific recombinase structure and function:crystal structure and activity of trimeric Cre recombinase bound to a three-way Lox DNA junction. J. Mol. Bio. 313:49-69