William M. Atkins
Professor, Department of Medicinal Chemistry
winky@u.washington.edu
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The general theme of research in my laboratory involves the study of structure
and function of proteins, with a particular emphasis on the mechanism of drug
metabolizing enzymes and protein engineering of oligomeric enzymes or peptides
with novel self-assembly properties. Our ultimate goals include design of drugs,
biomaterials, and nanodevices. A multidisciplinary approach is used, including
recombinant DNA methods, protein chemistry, biophysical methods and spectroscopic
techniques.
Partial List of
Recent Publications:
- Shanker, R. and Atkins, W. M. (1996) "Luciferase-dependent Cytochrome P450-catalyzed
Dehalogenation in Genetically Engineered Pseudomonas," Biotechnol. Progr.
12, 474 - 479.
- Dietze, E. C., Ibarra, C., Dabrowski, M. J., Bird, A. and Atkins, W. M.
(1996) "Rational Modulation of the Catalytic Activity of Glutathione S-Transferase
A1-1: Evidence for Incorporation of an On-face (pi * * * HO) Hydrogen Bond
at Tyrosine-9," Biochemistry 35, 11938-11944.
- Cook, D. L. and Atkins, W. M. (1997) "Enhanced Detoxication due to Distributive
Catalysis and Toxic Thresholds: A Kinetic Analysis," Biochemistry 36, 10801-10806.
- Nieslanik, B. S. and Atkins, W. M. (1998) "Contribution of Linear Free
Energy Relationships to Isozyme- and pH-Dependent Substrate Specificity of
Glutathione S-Transferase: Comparison of Model Studies and Enzymatic Reactions,"J.
Am. Chem. Soc. 120, 6651-6660.
- Dabrowski, M. D., Chen, J. P., Shi, H., Chen, H. C. and Atkins, W. M. (1998)
"Strategies for Protein-based Nanofabrication: Ni2+-NTA as a Chemical
Mask to Control Biologically-imposed Symmetry," Chemistry & Biology 5,
689-697.
- Storch, E. M., Grinstead, J. S., Campbell, A. P., Daggett, V. and Atkins,
W. M. (1999) "Engineering Out Motion: A Surface Disulfide Bond Alters the
Mobility of Tryptophan 22 in Cytochrome b5 As Probed by
Time-Resolved Fluorescence and 1H NMR Experiments," Biochemistry
38, 5065-5075.
- Nieslanik, B. S., Dabrowski, M. J., Lyon, R. P. and Atkins, W. M. (1999)
"Stopped-Flow Kinetic Analysis of the Ligand-Induced Coil-Helix Transition
in Glutathione S-Transferase A1-1: Evidence for a Persistent Denatured
State," Biochemistry 38, 6971-6980.
- Schurke, P., Freeman, J. C., Dabrowski, M. J. and Atkins, W. M. (1999)
"Metal-dependent Self-assembly of Protein Tubes from Escherichia coli Glutamine
Synthetase,"J. Biol. Chem. 274, 27963-27968.
- Nieslanik, B. S., Atkins, W. M., (2000) "The Catalytic Tyr-9 of Glutathione S-transferase A1-1 Controls the Dynamics of the C Terminus," J. Biol. Chem., 275, 17447-17451.
- Wang, R. W., Newton, D. J., Liu, N., Atkins, W. M. and Lu, A. Y. H., (2000) "Human Cytochrome P-450 3A4: In Vitro Drug-Drug Interaction Patterns are Substrate-Dependent," Drug Metab. Dispos., 28, 360-366.
- Adman, E. T., LeTrong, I., Stenkamp, R. E., Nieslanik, B. S., Dietze, E.
C., Tai, G., Ibarra, C., and Atkins, W. M. (2001) "Localization of the C-terminus
of Rat Glutathione S-Transferase A1-1: Crystal Structure of Mutants W21F and
W21F/F220Y," Proteins 42, 192-200.
- Nieslanik, B. S., Ibarra, C., and Atkins, W. M. (2001) "The C-Terminus
of Glutathione S-Transferase A1-1 is Required for Entropically-Driven Ligand
Binding," Biochemistry 40, 3536-3543.
- Atkins, W. M., Wang, R. W., and Lu, A. Y. H. (2001) "Allosteric Behavior
in Cytochrome P450-Dependent in Vitro Drug-Drug Interactions: A Prospective
Based on Conformational Dynamics," Chem. Res. Toxicol. 14, 338-347.
- Lyon, R. P. and Atkins, W. M. (2001) "Self-Assembly and Gelation of Oxidized
Glutathione in Organic Solvents," J. Am. Chem. Soc. 123, 4408-4413.
- Ibarra, C., Nieslanik, B. S. and Atkins, W. M. (2001) "Contribution of Aromatic-Aromatic Interactions to the Anomalous pKa of Tyr-9 and the C-terminal Dynamics of Glutathione S-Transferase A1-1," Biochemistry 40, 10614-10624.
- Atkins, W.M., Lu, W.D. and Cook, D.L. (2002) "Is there a toxicological advantage for non-hyperbolic kinetics in cytochrome P450 catalysis? Functional allostery from "distributive catalysis," J Biol Chem 277, 33258-33266.
- Le Trong, I., Stenkamp, R.E., Ibarra, C., Atkins, W.M. and Adman, E.T. (2002) "1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site," Proteins 48, 618-627.
- Lyon, R.P. and Atkins, W.M. (2002) "Kinetic characterization of native and cysteine 112-modified glutathione S-transferase A1-1: reassessment of nonsubstrate ligand binding," Biochemistry 41, 10920-10927.
- Dabrowski, M.J., Schrag, M.L., Wienkers, L.C. and Atkins, W.M. (2002) "Pyrene.pyrene complexes at the active site of cytochrome P450 3A4: evidence for a multiple substrate binding site," J Am Chem Soc 124, 11866-11867.
- Sukumaran, S., Atkins, W.M. and Shanker, R. (2002) "Engineering cytochrome
P-450s: chimeric enzymes," Appl Biochem Biotechnol 103, 291-30.
- Ibarra, C.A., Chowdhury, P., Petrich, J.W. and Atkins, W.M. (2003) "The anomalous pKa of Tyr-9 in glutathione S-transferase A1-1 catalyzes product release," J Biol Chem. (in press).
Atkins' Lab graphics designed by M. Dabrowski using MidasPlusTM
and GifBuilder 0.5 (copyright 1995-1997 Yves Piguet : piguet@ia.epfl.ch)
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This page last updated: September 10, 2008