Free-Energy Profile Analysis of the Catalytic Reaction of Glycinamide Ribonucleotide Synthetase.

ABSTRACT: The second step in the de novo biosynthetic pathway of purine is catalyzed by PurD, which consumes an ATP molecule to produce glycinamide ribonucleotide (GAR) from glycine and phosphoribosylamine (PRA). PurD initially reacts with ATP to produce an intermediate, glycyl-phosphate, which then reacts with PRA to produce GAR. The structure of the glycyl-phosphate intermediate bound to PurD has not been determined. Therefore, the detailed reaction mechanism at the molecular level is unclear. Here, we developed a computational protocol to analyze the free-energy profile for the glycine phosphorylation process catalyzed by PurD, which examines the free-energy change along a minimum energy path based on a perturbation method combined with the quantum mechanics and molecular mechanics hybrid model.

SUBMITTER: Yamamoto N 

PROVIDER: S-EPMC8880213 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature