Facebook-Icon linkedin logo “Twitter-Icon” gift
Font Size
   

William Atkins

Professor Bill Atkins
Sid Nelson Endowed Professor of Medicinal Chemistry
PH: 206 685 0379
winky@uw.edu


Lab Website

Education

  • BS in Chemistry, The College of William and Mary
  • MA in Pharmacology, Harvard University
  • PhD in Biochemistry, The University of Illinois
  • Postdoctoral Studies in Protein Dynamics, Penn State University

Research Interests

  • Structure-function mechanism of glutathione S-transferases and cytochrome P450
  • Protein engineering of supramolecular aggregates


Biography


Dr. Atkins is a biophysical enzymologist with two primary areas of interest. One area of research focus includes mechanisms of detoxication enzymes and transporters, which play critical roles in drug metabolism, drug-drug interactions, and interindividual responses to drugs. These enzymes are a fascinating variation on "traditional" enzymes because they have no defined substrates but instead have evolved to recognize a broad range of structurally diverse substrates. Atkins utilizes a combination of spectroscopic methods, mass spectrometry, chemical synthesis, computational methods, and molecular biology techniques to study the structure-function relationships of these enzymes, including Cytochrome P450s (CYPs), glutathione s-transferases (GSTs), and P-glycoprotein (P-gp).

The second area of interest includes therapeutic proteins, such as those used to treat various cancers and autoimmune diseases. The Atkins lab has recently moved into this research field and studies biophysical properties of antibody-drug conjugates and fusion proteins to understand the factors that determine their stability in serum and their interactions with their targets. Taken together, the research projects in the Atkins lab aim to improve the utility of small molecule drugs or biologics.

This research prepares students and postdoctoral scientists for careers in the pharmaceutical industry, the biotechnology sector and academia.



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.


Back to Medicinal Chemistry Faculty