• Postdoctoral Fellow, Albert Einstein College of Medicine, 2004-2009
• PhD, University of British Columbia, 2004
• Postdoctoral Fellow, Albert Einstein College of Medicine, 2004-2009

• National Science Foundation CAREER Award, 2013
  
• DuPont Young Professor Award, 2012
  
• Natural Science and Engineering Research Council (NSERC) Scholarship, 1999

• 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.

* Authors contributed equally

• Pham, T.V.; Murkin, A.S.; Moynihan, M.M.; Harris, L.; Tyler, P.C.; Shetty, N.; Sacchettini, J.C.; Huang, H.-L. A; Meek, T.D. Mechanism-based Inactivator of Isocitrate Lyases 1 and 2 from Mycobacterium Tuberculosis. Proc Nat Acad Sci. 2017, 114, 7617-7622.
• Kholodar, S.A.; Allen, C.L.; Gulick, A.M.; Murkin, A.S. The Role of Phosphate in a Multistep Enzymatic Reaction: Comparison of Reactions of the Substrate and Intermediate in Pieces. J Am Chem Soc 2015, 137, 2748-2756.
• Murkin, A.S.; Manning, K.A.; Kholodar, S.A. Mechanism and Inhibition of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase. Bioorg Chem 2014, 57, 171-185.
• Kholodar, S.A.*; Tombline, G.*; Liu, J.; Tan, Z.; Allen, C.L.; Gulick, A.M.; Murkin, A.S. Alteration of the Flexible Loop in 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase Boosts Enthalpy-Driven Inhibition by Fosmidomycin. Biochemistry 2014, 53, 3423-3431.
• Moynihan, M.M.; Murkin, A.S. Cysteine Is the General Base That Serves in Catalysis by Isocitrate Lyase and in Mechanism-Based Inhibition by 3-Nitropropionate. Biochemistry 2014, 53, 178-187.
• Kholodar, S.A.; Murkin, A.S. DXP Reductoisomerase: Reaction of the Substrate in Pieces Reveals a Catalytic Role for the Non-reacting Phosphodianion Group. Biochemistry 2013, 52, 2302-2308.
• Manning, K.A.; Sathyamoorthy, B.; Eletski, A.; Szyperski, T.; Murkin, A.S. Highly Precise Measurement of Kinetic Isotope Effects Using ¹H-Detected 2D [¹³C,¹H]-HSQC NMR Spectroscopy. J Am Chem Soc 2012, 134, 20589-20592.