Andrew S. Murkin
Phone: (716) 645-4249
Fax: (716) 645-6963
- 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:
- DuPont Young Professor Award, 2012-2015
- Natural Science and Engineering Research Council (NSERC) Scholarship, 1999-2001
- Enzyme mechanisms
- Determination of transition-state structures of enzyme-catalyzed reactions
- Synthesis of enzyme inhibitors
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:
- Liu, J.; *Murkin, A.S. Pre-Steady-State Kinetic Analysis of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase from Mycobacterium tuberculosis Reveals Partially Rate-Limiting Product Release by Parallel Pathways Biochemistry 2012, ASAP.
- Cassera, M.B.; Hazleton, K.Z.; Merino, E.F.; Obaldia III, N.; Ho, M.-C.; Murkin, A.S.; DePinto, R.; Gutierrez, J.A.; Almo, S.C.; Evans, G.B.;Babu, Y.S.; Schramm, V.L. Plasmodium falciparum Parasites are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model PLoS ONE 2011, 6, e26916.
- Silva, R.G.; Murkin, A.S.; Schramm, V.L. Femtosecond Dynamics Coupled to Chemical Barrier Crossing in a Born-Oppenheimer Enzyme Proc. Natl. Acad. Sci. USA 2011, 108, 18661.
- Silva, R.G.; Hirschi, J.S.; Ghanem, M.; Murkin, A.S.; Schramm, V.L. Arsenate and Phosphate as Nucleophiles at the Transition States of Human Purine Nucleoside Phosphorylase Biochemistry 2011, 50, 2701.
- Murkin, A.S.; Schramm, V.L. Purine Nucleoside Phosphorylases as Targets for Transition-State Analog Drug Design. In Drug Design: Structure- and Ligand-Based Approaches; Merz, K.M.; Reynolds, C.H.; Ringe, D., Eds.; Cambridge University Press: Cambridge, 2010; pp 215-247.
- Ghanem, M.*; Murkin, A.S.*; Schramm, V.L. Ribocation Transition State Capture and Rebound in Human Purine Nucleoside Phosphorylase Chem. Biol. 2009, 16, 971. (*Both authors contributed equally).
- 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).
- 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.
- 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.
For more of Andrew Murkin's Publications, please click here.