The catalytic activity of proline racemase: a quantum mechanical/molecular mechanical study

J Phys Chem B. 2008 Jan 31;112(4):1057-9. doi: 10.1021/jp7104105. Epub 2007 Nov 29.

Abstract

The enzyme proline racemase from the eukaryotic parasite Trypanosoma cruzi (responsible for endemic Chagas disease) catalyzes the reversible stereoinversion of chiral Calpha in proline. We employed a new combined quantum mechanical and molecular mechanical (QM/MM) potential to study the reaction mechanism of the enzyme. Three critical points were found: two almost isoenergetic minima (M1a and M2a), in which the enzyme is bound to L- and D-Pro, respectively, and a transition state (TSCa), unveiling a highly asynchronous concerted process. A systematic analysis was performed on the optimized geometries to point out the key role played by some residues in stabilizing the transition state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Isomerases / chemistry*
  • Amino Acid Isomerases / metabolism*
  • Catalysis
  • Molecular Structure
  • Quantum Theory

Substances

  • Amino Acid Isomerases
  • proline racemase