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Department of Anesthesiology- Research Division |
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Research Interests: The major interest of Dr. Waskell's laboratory is to understand the biochemical mechanisms by which the body degrades anesthetics and drugs. We are particularly interested in understanding how cytochrome b5 augments cytochrome P450 catalyzed drug metabolism. The cytochromes P450 are a family of enzymes that are responsible for the metabolism of the vast majority of drugs metabolized by humans. Many of our experiments use the techniques of molecular biology and biochemistry to study the molecular details of the interaction of cytochrome P450 with its redox partners cytochrome b5 and cytochrome P450 reductase. We have recently shown that breakdown of drugs by microsomal cytochromes P450 proceeds via a long-lived intermediate which we are currently attempting to identify. A second interest in the laboratory is drug-drug interactions. Recent Publications: Mak PJ, Im SC , Zhang H., Waskell L, Kincaid JR. Resonance Raman studies of cytochrome P450 2B4 in its interactions with substrates and redox partners. Biochemistry 47(12): 3950-3963, Mar 25, 2008. [PubMed] Zhang H, Hamdane D, Im SC , Waskell L. Cytochrome b5 inhibits electron transfer from NADPH-cytochrome P450 reductase to ferric cytochrome P450 2B4. J Biol Chem, 283(9): 5217-5225. Feb, 29, 2008. [PubMed] Lin HL, Myshkin E, Waskell L. Peroxynitrite activation of human cytochrome P450s 2B6 and 2E1: heme modification and site-specific nitrotyrosine formation. Chem Res Toxicol 20(11):1612-22, Nov. 2007 [PubMed] Zhang H, Im S-C, Waskell L. Cytochrome b5 increases the rate of product formation by cytochrome P450 2B4 and competes with cytochrome P450 reductase for a binding site on cytochrome P450 2B4. J Biol Chem 282(41): 29766-76, Oct. 12, 2007 [PubMed] Durr UHN, Waskell L, Ramamoorthy A. The cytochromes P450 and b5 and their reductases-Promising targets for structural studies by advanced solid-state NMR spectroscopy. Biochim Biophys Acta. 1768(12):3235-59. Aug. 24 2007 [PubMed] Durr UHN, Yamamoto K, Im SC, Waskell L, Ramamoorthy A. Solid-state NMR reveals structural and dynamical properties of a membrane-anchored electron-carrier protein, cytochrome b(5). Journal of the American Chemical Society, 129 (21): 6670-1 May 30 2007. [PubMed] Kobayashi Y, Sridar C, Kent UM, Puppali SG, Rimoldi JM, Zhang H, Waskell L, Hollenberg PF. Structure-Activity Relationship and Elucidation of the Determinant Factor(s) Responsible for the Mechanism-Based Inactivation of P450 2B6 by Substituted Phenyl Diaziridines. Drug Metab Dispos. 34:2102-10, 2006. [PubMed] Z hang H, Myshkin E, Waskell L. Role of cytochrome b5 in catalysis by cytochrome P450 2B4. Biochemical and Biophysical Research Communications 338: 449-506, 2005. [PubMed] Lin HL, Zhang H, Waskell L, Hollenberg PF. The highly conserved Glu149 and Tyr190 residues contribute to peroxynitrite-mediated nitrotyrosine formation and the catalytic activity of cytochrome P450 2B1. Chem Res Toxicol 18: 1203-10, 2005. [PubMed] Deep S, Im SC, Zuiderweg ER, Waskell L. Characterization and calculation of a cytochrome c-cytochrome b(5) complex using NMR data. Biochemistry 44: 10654-68, 2005. [PubMed] Cournoyer JJ, Pitman JL, Ivleva VB, Fallows E, Waskell L, Costello CE, O'Connor PB. Deamidation: Differentiation of aspartyl from isoaspartyl products in peptides by electron capture dissociation. Protein Science 14:452-463, 2005. [PubMed] Research Divisions | ||||||
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