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 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.
Stenta
Marco
M
Dipartimento di Chimica G. Ciamician, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy.
Calvaresi
Matteo
M
Altoè
Piero
P
Spinelli
Domenico
D
Garavelli
Marco
M
Bottoni
Andrea
A
D000591:Amino Acid Isomerases / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D015394:Molecular Structure; D011789:Quantum Theory
D000591:Amino Acid Isomerases; C022451:proline racemase