The Catalytic Activity of Proline Racemase:  A Quantum Mechanical/Molecular Mechanical Study.

The enzyme proline racemase from the eukaryotic parasite Trypanosoma cruzi(responsible for endemic Chagas disease) catalyzes the reversible stereoinversion of chiral Cin 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 (M1aand 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. [ABSTRACT FROM AUTHOR]