The Department of Chemistry

Faculty

Andrew S. Murkin

 

Andrew 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:

  • National Science Foundation CAREER Award (2013)

  • DuPont Young Professor Award (2012)

  • Natural Science and Engineering Research Council (NSERC) Scholarship (1999)

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:

* Authors contributed equally

  1. Murkin, A.S.; Manning, K.A.; Kholodar, S.A. Mechanism and Inhibition of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase. Bioorg Chem 2014, doi:10.1016/j.bioorg.2014.06.001.
  2. 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 201453, 3423-3431.
  3. Murkin, A.S.; Moynihan, M.M. Transition-State-Guided Drug Design for Treatment of Parasitic Neglected Tropical Diseases. Curr Med Chem 201421, 1781-1793.
  4. 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 201453, 178-187.
  5. 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 201352, 2302-2308.
  6. 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 2012134, 20589-20592.
  7. Liu, J.; Murkin, A.S. Pre-Steady-State Kinetic Analysis of 1-Deoxy-D-xylulose-5-phosphate Reductoisomerase from Mycobacterium tuberculosis Reveals Rate-Limiting Product Release by Parallel Pathways. Biochemistry 201251, 5307-5319.

For more of Andrew Murkin's Publications, please click here.

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The Department of Chemistry