Mechanism of Triphosphate Hydrolysis by Human MAT2A at 1.07 A Resolution.

ABSTRACT: Human methionine adenosyltransferase MAT2A provides S-adenosyl-l-methionine (AdoMet) for methyl-transfer reactions. Epigenetic methylations influence expression patterns in development and in cancer. Transition-state analysis and kinetic studies have described the mechanism of AdoMet and triphosphate formation at the catalytic site. Hydrolysis of triphosphate to pyrophosphate and phosphate by MAT2A is required for product release and proceeds through a second chemical transition state. Crystal structures of MAT2A with analogues of AdoMet and pyrophosphate were obtained in the presence of Mg²⁺, Al³⁺, and F^-. MgF₃^- is trapped as a PO₃^- mimic in a structure with malonate filling the pyrophosphate site. NMR dem

SUBMITTER: Ghosh A 

PROVIDER: S-EPMC9228670 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature