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