Offices and Labs
Profile IntroductionStructural 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.
|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|
Structural Biochemistry, Enzymology and Protein Engineering of Protein-nucleic acid Interactions
1) Mechanism and regulation of E. coli Cytidine Triphosphate Synthetase
2) Regulation and dynamic localization of human CTP synthetases
Department and Center Affiliations
CBS Grad Group Affiliations
Specialties / Focus
- Cell Biology
- Structural Biology
Graduate Groups not Housed in CBS
Shelley Martin (1997-2007), Kathy Gelato (2001-2007), Hanseong Kim (2001-2005), Dr. James Endrizzi (2002-2006), Lesley Steinman (2004-2007), Roger Jessinghaus (2008-), Ria Suri (2013-2014), Bryan Teefy (2014-15 ), Robert Ovadia (2010-2012), Chris Habrian (2012-2014), Adithi Chandrasekhara (2013-2014), Jacob Dinis (2013-), Christina Bui (2014-), Bita Shahrvini (2014-),
Lynch EM, Hicks DR, Shepherd M, Endrizzi JA, Maker A, Hansen JM, Barry RM, Gitai Z, Baldwin EP, Kollman JM. (2017) Human CTP synthase filament structure reveals the active enzyme conformation. Nature structural & molecular biology 24(6):507-514.
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