title: Ab initio QM/MM studies of the phosphoryl transfer reaction catalyzed by PEP mutase suggest a dissociative metaphosphate transition state.
abstract: 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.
authors.affiliation: Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, USA.
authors.forename: Dingguo
authors.initials: D
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D008956:Models, Chemical; D008958:Models, Molecular; D010728:Phosphoenolpyruvate / Q000737:chemistry*; D010757:Phosphorous Acids / Q000737:chemistry*; D017875:Phosphotransferases (Phosphomutases) / Q000737:chemistry*; D011773:Pyruvates / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: C026220:3-phosphonopyruvate; D010757:Phosphorous Acids; D011773:Pyruvates; D010728:Phosphoenolpyruvate; D017875:Phosphotransferases (Phosphomutases); C057167:phosphoenolpyruvate mutase; C043639:metaphosphoric acid