Goodin, David B. - University of California, Davis

个人简介

Appointed to UC Davis faculty (2011) Associate Professor, The Scripps Research Institute, La Jolla, CA (1994-2011) Assistant Professor, The Scripps Research Institute, La Jolla, CA (1987-94) NIH Postdoctoral Fellow, University of British Columbia, Vancouver, Canada (1983-87) Ph.D. University of California, Berkeley (1983) B.S. University of Oklahoma (1978)

研究领域

Bioinorganic Chemistry/Biophysical Chemistry/Chemical Biology

Our research is focused on understanding how metalloenzymes operate. We are interested in defining the mechanism and reactive intermediates used by oxidative heme enzymes such as cytochrome P450, nitric oxide synthase and peroxidases. These enzymes utilize O2 to generate highly reactive intermediates containing hypervalent iron and radical species (Fe+4=O, R+.) to catalyze the hydroxylation of a huge variety of substrates. Understanding how nature controls and directs this reactivity is one of the main focuses of our work. Our laboratory is trying to determine how substrates are recognized by a particular P450 and how the structural changes are coupled to function. We are also working to re-engineer and evolve these enzymes to develop catalysts capable of oxidizing novel substrates. Our experimental approach involves the integrated use of multidisciplinary techniques including molecular biology, protein engineering, x-ray crystallography, electron paramagnetic resonance, electrochemistry, calorimetry and kinetics. Engineered enzymes may have practical utility as bio-sensors, reagents for stereospecific chemical transformations and bio-remediation. More generally, our research may contribute to the understanding of metalloenzyme function, protein-ligand interactions, molecular recognition and drug design.

近期论文

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Myers, W.K., Lee, Y.-T., Britt, R. D. and Goodin, D.B. (2013) "The Conformation of P450cam in Complex with Putidaredoxin Is Dependent on Oxidation State", J. Am. Chem. Soc 135, 11732. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Barelier, S., Boyce, S.E., Fish, I., Fischer, M., Goodin, D.B., and Shoichet, B.K. (2013) "Roles for Ordered and Bulk Solvent in Ligand Recognition and Docking in Two Related Cavities", PLoS ONE 8, 69153. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stoll, S., Lee, Y.-T., Zhang, M., Wilson, R.F., Britt, R.D. and Goodin, D.B. (2012) "Double electron-electron resonance shows cytochrome P450cam undergoes a conformational change in solution upon binding substrate", Proc. Natl. Acad. Sci. USA, 109, 12888-12893. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Markwick, Phineus R.L., Pierce, Levi C.T., Goodin, David B. and McCammon, J. Andrew (2011) "Adaptive accelerated molecular dynamics reveals the molecular plasticity of P450cam", J. Phys. Chem. Lett., 2, 158-164. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lee, Y.-T., Glazer, E.C., Wilson, R.F., Stout, C.D. and Goodin, D.B. (2011) "Three clusters of conformational states in P450cam reveal a multi-step pathway for closing of the substrate access channel", Biochemistry, 50, 693-703. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Jensen, G.M. and Goodin, D.B. (2011) "Impact of proximal and distal pocket site-directed mutations on the ferric/ferrous heme redox potential of yeast cytochrome c peroxidase", Theor. Chem. Acc., 130, 1185-1196. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nigro, A.P., and Goodin, D.B. (2010) "Reaction of N-hydroxyguanidine with the ferrous-oxy state of a heme peroxidase cavity mutant: A model for the reactions of nitric oxide synthase", Arch. Biochem. Biophys., 500, 66-73. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lee, Y.-T., Wilson, R.F., Rupniewski, I. and Goodin, D.B. (2010) "P450cam visits an open conformation in the absence of substrate", Biochemistry 49, 3412-3419. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Annalora, A. J., Goodin, D.B., Hong, W.-X., Zang, Q., Johnson, E.F., Stout, C.D. (2010) "Crystal Structure of CYP24A1, a Mitochondrial Cytochrome P450 Involved in Vitamin D Metabolism", J. Mol. Biol. 396, 441-451. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Putnam, A.-M. A. H., Lee, Y.-T. and Goodin D.B. (2009) "Replacement of an Electron Transfer Pathway in Cytochrome c Peroxidase with a Surrogate Peptide", Biochemistry, 48, 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vetter, Stefan W., Terentis, A.C., Osborne, R., Dawson, J.H. and Goodin, D.B. (2009) "Replacement of the Axial Histidine Heme Ligand with Cysteine in Nitrophorin I: Spectroscopic and Crystallographic Characterization", J. Biol. Inorg. Chem, 14, 179. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Glazer, E.C., Le Nguyen, Y.H., Gray, H.B., and Goodin, D.B. (2008) "Probing Inducible Nitric Oxide Synthase with a Pterin-Ru(II) Sensitizer Wire", Angew. Chemie, 47, 898. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contakes, S.M., Nguyen, Y.H.L., Gray, H.B., Glazer, E.C., Hays, A.-M.A., and Goodin, D.B. (2006) "Conjugates of Heme-Thiolate Enzymes with Photoactive Metal-Diimine Wires", in Structure & Bonding, Springer-Verlag, Berlin/Heidelberg, 123,177. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Brenk, R., Vetter, S., Boyce, S.E., Goodin, D.B., and Shoichet, B. (2006) "Probing Molecular Docking in a Charged Model Binding Site," J. Mol. Biol, 357, 1449. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Udit, A.K., Belliston-Bittner, W., Glazer, E.C., Nguyen, Y.H.L., Gillan, J.M., Hill, M.G., Marletta, M.A., Goodin, D.B., Gray, H.B. (2005) "Redox Couples of Inducible Nitric Oxide Synthase," J. Am. Chem. Soc 127, 11212. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hays, A.-M.A., Dunn, A.R., Chiu, R., Gray, H.B., Stout, C.D., and Goodin, D.B. (2004) "Conformational States of Cytochrome P450cam Revealed by Trapping of Synthetic Molecular Wires," J. Mol. Biol 344, 455. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kroeck, L., Shivanyuk, A., Goodin, D.B., and Rebek, J., Jr. (2004) "Spin Labeling Monitors Weak Host-Guest Interactions," Chemical Communications 3, 272. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rosenfeld, R.J., Goodsell, D.S., Musah, R.A., Morris, G.M., Goodin, D.B., and Olson, A.J. (2003) "Automated Docking of Ligands to an Artificial Active Site: Augmenting Crystallographic Analysis with Computer Modeling," Journal of Computer-Aided Molecular Design 17, 525. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Voegtle, H.L., Sono, M., Adak, S., Pond, A.E., Tomita, T., Perera, R., Goodin, D.B., Ikeda-Saito, M., Stuehr, D.J., and Dawson, J.H. (2003) "Spectroscopic Characterization of Five- and Six-Coordinate Ferrous-NO Heme Complexes. Evidence for Heme Fe- Proximal Cys Bond Cleavage in the Ferrous-NO Adducts of the Trp-409Tyr/Phe Proximal Environment Mutants of Neuronal NOS," Biochemistry 42, 2475. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hays, A.-M.A., Gray, H.B., and Goodin, D.B. (2003) "Trapping of Peptide-Based Surrogates in an Artificially Created Channel of Cytochrome c Peroxidase," Protein Science 12, 278.