The catalytic activity of proline racemase: a quantum mechanical/molecular mechanical study
Marco Stenta1, Matteo Calvaresi, Piero Altoè
1Dipartimento di Chimica G. Ciamician, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy.
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.
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