Faculty

Andrew S. Murkin

Assistant Professor
Office: NSC 672 Natural Sciences Complex

Phone: (716) 645-4249

Fax: (716) 645-6963

E-mail: amurkin@buffalo.edu

Education:

B. S., University of British Columbia (1998)
Ph.D., University of British Columbia (2004)
Postdoctoral Fellow, Albert Einstein College of Medicine (2004-09)

Honors and Awards:

Natural Science and Engineering Research Council (NSERC) Scholarship, 1999-2001

Specializations:

Enzyme mechanisms
Determination of transition-state structures of enzyme-catalyzed reactions
Synthesis of enzyme inhibitors

Research Summary:

The primary goal of research in the Murkin Laboratory is to understand the mechanisms of enzymatic processes related to disease and to construct models of their transition states, which may serve as blueprints for drug design. This “rational approach” has proven effective in the development of powerful enzyme inhibitors that have been successful in clinical treatments of human disorders. Our research aims to conquer these biological challenges while simultaneously addressing fundamentals of enzyme theory.

Transition-state structures are determined using multiple kinetic isotope effects (KIEs), which are measures of the bonding changes a substrate undergoes as it traverses through the transition state of a reaction. A transition-state model is generated by matching experimental KIEs to those calculated using computation. This model serves as a blueprint for the design of transition-state analogues, which are among the most powerful inhibitors in nature.

In the Murkin Laboratory, students will gain expertise in many of the chemical, biochemical, and biophysical tools essential for pursuing careers in academia or industry. Among these methods are protein expression, enzyme kinetics, and synthesis of inhibitors and isotopically labeled compounds. Projects in our lab are directed at drug targets in infectious diseases including malaria, tuberculosis, and bacterial infections.

Selected Recent Publications:

Clinch, K.; Evans, G.B.; Furneaux, R.H.; Kelly, P.M.; Legentil, L.; Murkin, A.S.; Li, L.; Schramm, V.L.; Tyler, P.C.; Woolhouse, A.D. Third Generation Immucillins: Acyclic Immucillins as Inhibitors of Purine Nucleoside Phosphorylase J. Med. Chem. 2009, ASAP; 10.1021/jm801421q.
Murkin, A.S.; Clinch, K.; Mason, J.M.; Tyler, P.C.; Schramm, V.L. Immucillins in Custom Catalytic-Site Cavities Bioorg. Med. Chem. Lett. 2008, 18, 5900 (Special issue invitation).
Mason, J.M.; Murkin, A.S.; Li, L.; Schramm, V.L.; Gainsford, G.J.; Skelton, B.W. A ß-Fluoroamine Inhibitor of Purine Nucleoside Phosphorylase J. Med. Chem. 2008, 51, 5880.
Evans, G.B.; Furneaux, R.H.; Greatrex, B.; Murkin, A.S.; Schramm, V.L.; Tyler, P.C. Azetidine Based Transition State Analogue Inhibitors of N-Ribosyl Hydrolases and Phosphorylases J. Med. Chem. 2008, 51, 948.
Murkin, A.S.; Tyler, P.C.; Schramm, V.L. Transition State Interactions Revealed in Purine Nucleoside Phosphorylase by Binding Isotope Effects J. Am. Chem. Soc. 2008, 130, 2166.
Rinaldo-Matthis, A.; Murkin, A.S.; Ramagopal, U.; Clinch, K.; Mee, S.P.H.; Evans, G.B.; Tyler, P.C.; Furneaux, R.H.; Almo, S.C.; Schramm, V.L. L-Enantiomers of Transition State Analogue Inhibitors Bound to Human Purine Nucleoside Phosphorylase J. Am. Chem. Soc. 2008, 130, 842.
Murkin, A.S.; Birck, M.R.; Rinaldo-Matthis, A.; Shi, W.; Taylor, E.A.; Almo, S.C.; Schramm, V.L. Neighboring Group Participation in the Transition State of Human Purine Nucleoside Phosphorylase Biochemistry 2007, 46, 5038.
Deng, H.; Murkin, A.S.; Schramm, V.L. Phosphate Activation in the Ground State of Purine Nucleoside Phosphorylase J. Am. Chem. Soc. 2006, 128, 7765.
Taylor Ringia, E.A.; Tyler, P.C.; Evans, G.B.; Furneaux, R.H.; Murkin, A.S.; Schramm, V.L. Transition State Analogue Discrimination by Related Purine Nucleoside Phosphorylases J. Am. Chem. Soc. 2006, 128, 7126.