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

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.

• Authors: Marco Stenta, Matteo Calvaresi, Piero Altoè, Domenico Spinelli, Marco Garavelli, Andrea Bottoni
• Journal: The journal of physical chemistry. B (J Phys Chem B) Vol. 112 Issue 4 Pg. 1057-9 (Jan 31 2008) ISSN: 1520-6106 [Print] United States
• PMID: 18044876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Isomerases
• proline racemase

Topics

• Amino Acid Isomerases (chemistry, metabolism)
• Catalysis
• Molecular Structure
• Quantum Theory