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.
Education, Awards and Professional Highlights
- 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 (1987-1994)
- NIH Postdoctoral Fellow, University of British Columbia, Vancouver, Canada (1983-1987)
- Ph.D. University of California, Berkeley (1983)
- B.S. University of Oklahoma (1978)
- 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.
- 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.
- 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. (2007) “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.