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University of Washington
Saturday May 25 , 2013
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William Atkins

Professor Bill Atkins
Professor of Medicinal Chemistry
PH: 206 685 0379
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Lab Website

ACADEMIC BIO

  • B.S. in Chemistry, The College of William and Mary, 1980.
  • M.A. in Pharmacology, Harvard University, 1983.
  • Ph.D. in Biochemistry, The University of Illinois, 1989.
  • Postdoctoral Studies in Protein Dynamics, Penn State University, 1988-1991.


RESEARCH OVERVIEW

Our lab studies enzymes and proteins that participate in the detoxification of foreign chemicals, including therapeutic drugs. We are fascinated by enzymes that can metabolize many structurally unrelated substrates, because this behavior defies "traditional" views of enzymology. We are also studying therapeutic antibodies and other pharmaceutically important proteins, to understand structure-function aspects of their tissue targeting, clearance, and in vitro stability. Taken together, these research areas provide a wide-ranging blend of methodologies and experimental approaches that train undergraduates, graduate students, and post-doctoral fellows for careers in biotechnology, the pharmaceutical industry, and related areas of academic research. We utilize a diverse array of biophysical, chemical, and biological approaches, to understand these enzymes and proteins in the context of systems biology. Our lab values broad training and collaborative research. Students are encouraged to indentify and learn the methods that best illuminate their specific projects, rather than rely solely on methods established by other lab members.


RECENT SELECTED PUBLICATIONS

  • Zhao C, Gao Q, Roberts AG, Shaffer SA, Doneanu CE, Xue S, Goodlett DR, Nelson SD, Atkins SM. "Cross-linking mass spectrometry and mutagenesis confirm the functional importance of surface interactions between CYP3A4 and holo/apo cytochrome b(5)."  Biochemistry 51(47):9488-500; ePub Nov 14 (2012).
  • Conner KP, Vennam P, Woods CM, Krzyaniak MD, Bowman MK, Atkins WM. "1,2,3-Triazole-heme interactions in cytochrome P450: functionally competent triazole-water-heme complexes." Biochemistry 51(32):6441-57. ePub Jul 31 (2012).
  • Acchione M, Kwon H, Jochheim CM, Atkins WM.  "Impact of linker and conjugation chemistry on antigen binding, Fc receptor binding and thermal stability of model antibody-drug conjugates."  MAbs 4(3); epub Apri 26 (2012).  PubMed link.
  • Ritchie TK, Kwon HW, Atkins WM.  "Conformational Analysis of Human ATP-Binding Cassette Transporter ABCB1 in Lipid Nanodiscs and Inhibition by the Antibodies MRK16 and UIC2."  J Biol Chem, 286(45):39489-96 (2011).  PubMed link.
  • Balogh LM, Atkins WM. "Interactions of glutathione transferases with 4-hydroxynonenal." Drug Metab Rev. 43(2):165-78 (2011).
  • Honaker MT, Acchione M, Sumida JP, Atkins WM. "Ensemble Perspective for Catalytic Promiscuity: Calorimetric Analysis of the Active Site Conformational Landscape of a Detoxification Enzyme." J Biol Chem. 286(49):42770-6 (Dec 9, 2011).  PubMed link.
  • Conner KP, Woods CM, Atkins WM. "Interactions of cytochrome P450s with their ligands." Arch Biochem Biophys. 507(1):56-65 (2011).
  • Atkins WM, Qian H. "Stochastic Ensembles, Conformationally Adaptive Teamwork, and Enzymatic Detoxification." Biochemistry, 50(19):3866-72 (2011).  PubMed link.
  • Foti RS, Honaker M, Nath A, Pearson JT, Buttrick B, Isoherranen N, Atkins WM. "Catalytic versus Inhibitory Promiscuity in Cytochrome P450s: Implications for Evolution of New Function." Biochemstry (New Concepts). 50:2387-2393 (2011).
  • Yang J, Atkins WM, Isoherranen N, Paine MF, Thummel KE. "Evidence of CYP3A Allosterism in Vivo: Analysis of Interaction Between Fluconazole and Midazolam." Clin Pharmacol Ther., 91(3):442-9 (2011).  PubMed link.
  • Woods CM, Fernandez C, Kunze KL, Atkins WM. "Allosteric activation of cytochrome P450 3A4 by α-naphthoflavone: branch point regulation revealed by isotope dilution analysis." Biochemistry. 50(46):10041-51 (Nov 22 2011).  PubMed link.
  • Kim J, Park HC, Gedi V, Park HY, Roberts AG, Atkins WM, Yoon MY. "Yeast-Hybrid Based High-Throughput Assay for Identification of Anthrax Lethal Factor Inhibitors." Biochem Biophys Res Commun. (2010 Dec 6) Epub ahead of print.
  • Nath A, Zientek MA, Burke BJ, Jiang Y, Atkins WM. "Quantifying and Predicting the Promiscuity and Isoform Specificity of Small-Molecule Cytochrome P450 Inhibitors." Drug Metab Dispos. 38(12):2195-203 (2010 Dec) Epub 2010 Sep 14.
  • Shireman LM, Kripps KA, Balogh LM, Conner KP, Whittington D, Atkins WM. "Glutathione Transferase A4-4 Resists Adduction by 4-Hydroxynonenal." Arch Biochem Biophys. 504(2):182-9 (2010 Dec 15) Epub 2010 Sep 15.
  • Roberts AG, Cheesman MJ, Primak A, Bowman MK, Atkins WM, Rettie AE. "Intramolecular Heme Ligation of the Cytochrome P450 2C9 R108H Mutant Demonstrates Pronounced Conformational Flexibility of the B-C Loop Region: Implications for Substrate Binding." Biochemistry. 49(40):8700-8708 (2010 Oct 12) Epub 2010 Sep 21.
  • Dabrowski MJ, Zolnerciks JK, Balogh LM, Greene RJ, Kavanagh TJ, Atkins WM. "Stereoselective Effects of 4-Hydroxynonenal in Cultured Mouse Hepatocytes." Chemical Res Toxicol. (2010 Sep 28) Epub ahead of print.


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