A binuclear metallohydrolase model for RelA/SpoT-Homolog (RSH) hydrolases.

ABSTRACT: When challenged by starvation, bacterial organisms synthesize guanosine pentaphosphate and tetraphosphate, collectively denoted as (p)ppGpp, as second messengers to reprogram metabolism toward slower growth and enhanced stress tolerance. When starvation is alleviated, the RelA-SpoT Homolog (RSH) hydrolases downregulate (p)ppGpp, cleaving the 3'-diphosphate to produce GTP or GDP. Metazoan RSH hydrolases possess phosphatase activity responsible for converting cytoplasmic NADPH to NADH in mammalian cells. Inhibitor development for this family may therefore provide therapies to combat bacterial infection or metabolic dysregulation. Despite the availability of dozens of high-resolution structures, catalytic mechanisms of RSH hydrolases have remained poorly understood. All RSH hydrolases tightly

SUBMITTER: Zhou RW 

PROVIDER: S-EPMC11554896 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature