Phosphate Binding in PNP Alters Transition-State Analogue Affinity and Subunit Cooperativity.

ABSTRACT: Purine nucleoside phosphorylases (PNPs) catalyze the phosphorolysis of 6-oxypurine nucleosides with an HPO₄^2- dianion nucleophile. Nucleosides and phosphate occupy distinct pockets in the PNP active site. Evaluation of the HPO₄^2- site by mutagenesis, cooperative binding studies, and thermodynamic and structural analysis demonstrate that alterations in the HPO₄^2- binding site can render PNP inactive and significantly impact subunit cooperativity and binding to transition-state analogue inhibitors. Cooperative interactions between the cationic transition-state analogue and the anionic HPO₄^2- nucleophile demonstrate the importance of reforming the transition-state ensemble for optimal inhibition with trans

SUBMITTER: Minnow YVT 

PROVIDER: S-EPMC12906914 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature