Ab initio QM/MM studies of the phosphoryl transfer reaction catalyzed by PEP mutase suggest a dissociative metaphosphate transition state.

The interconversion between phosphoenolpyruvate (PEP) and phosphonopyruvate (P-pyr) catalyzed by PEP mutase is investigated using an ab initio QM/MM method with the QM region treated at the B3LYP/6-31G* level of theory. Two-dimensional minimum energy path calculations were carried out for both the wild-type enzyme and the N122A mutant. The calculations suggest a dissociative transition state featuring metaphosphate and Mg(2+)-coordinating pyruvate enolate, stabilized by an extensive hydrogen bond network involving Asn122, Ser123, Arg159, His190, Ser46, and Leu48. It is also found that a substantial conformational change in the pyruvyl group is required for the interconversion.