William Atkins

Sid Nelson Endowed Professor of Medicinal Chemistry

Atkins Lab, Department of Medicinal Chemistry, Medicinal Chemistry Faculty

Expertise: Biotechnology, Cytochrome P450, Drug Metabolism, Distribution and Transport

Telephone: (206) 685-0379

Email: winky@uw.edu

Website: Atkins Lab

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.

Selected Publications

  • Li MJ, Nath A, Atkins WM. “Differential Coupling of Binding, ATP Hydrolysis, and Transport of Fluorescent Probes with P-Glycoprotein in Lipid Nanodiscs.” Biochemistry. 2017 May 16;56(19):2506-2517. PubMed link.
  • Goulet DR, Zwolak A, Chiu ML, Nath A, Atkins WM. “Diffusion of Soluble Aggregates of THIOMABs and Bispecific Antibodies in Serum.” Biochemistry. 2017 May 2;56(17):2251-2260. PubMed link.
  • McClary WD, Sumida JP, Scian M, Paço L, Atkins WM. “Membrane Fluidity Modulates Thermal Stability and Ligand Binding of Cytochrome P4503A4 in Lipid Nanodiscs.” Biochemistry. 2016 Nov 15;55(45):6258-6268. PubMed link.
  • Scian M, Guttman M, Bouldin SD, Outten CE, Atkins WM. “The Myeloablative Drug Busulfan Converts Cysteine to Dehydroalanine and Lanthionine in Redoxins.” Biochemistry. 2016 Aug 23;55(33):4720-30. PubMed link.
  • Treuheit NA, Redhair M, Kwon H, McClary WD, Guttman M, Sumida JP, Atkins WM. “Membrane Interactions, Ligand- Dependent Dynamics, and Stability of Cytochrome P4503A4 in Lipid Nanodiscs.” Biochemistry. 2016 Feb 23;55(7):1058-69. PubMed link.
  • Scian M, Atkins WM. “The busulfan metabolite EdAG irreversibly glutathionylates glutaredoxins.” Arch Biochem Biophys. 2015 Oct 1;583:96-104. PubMed link.
  • Trahey M, Li MJ, Kwon H, Woodahl El, McClary WD, Atkins WM. “Applications of Lipid Nanodiscs for the Study of Membrane Proteins by Surface Plasmon Resonance.”Curr Protoc Protein Sci.2015 Aug3;81:29.13.1-16. PubMed link.
  • Conner KP, Cruce AA, Krzyaniak MD, Schimpf AM, Frank DJ, Ortiz de Montellano P, Atkins WM, Bowman MK. “Drug modulation of water-heme interactions in low-spin P450 complexes of CYP2C9d and CYP125A1.” Biochemistry 2015 Feb 10; 54(5):1198-207. PubMed link.
  • Atkins WM. “Biological messiness vs. biological genius: Mechanistic asepcts and roles of protein promiscuity.” J Steroid Biochem Mol Biol. 2014 Sep 12 [Epub ahead of print]. PubMed link.
  • Conner KP, Schimpf AM, Cruce AA, McLean KJ, Munro AW, Frank DJ, Krzyaniak MD, Ortiz de Montellano P, Bowman MK, Atkins WM. “Strength of axial water ligation in substrate-free cytochrome P450s is isoform dependent.” Biochemistry 2014 Mar 11; 53(9):1428-34. PubMed link.
  • Scian M, Acchione M, Li M, Atkins WM. “Reaction dynamics of ATP hydrolysis catalyzed by P-glycoprotien.” Biochemistry 2014 Feb 18; 53(6):991-1000. PubMed link.
  • Zhao C, Gao Q, Roberts AG, Shaffer SA, Doneanu CE, Xue S, Goodlett DR, Nelson SD, Atkins WM. “Cross-linking mass spectrometry and mutagenesis confirm the functional importance of surface interactions between CYP3A4 and holo/apo cytochrome b(5).” Biochemistry 2012 Nov 27; 51(47):9488-500. ACS link.
  • 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 2012 Aug 14;51(32):6441-57. ACS link.