Structure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery.

ABSTRACT: G-protein metallochaperone MeaB in bacteria [methylmalonic aciduria type A (MMAA) in humans] is responsible for facilitating the delivery of adenosylcobalamin (AdoCbl) to methylmalonyl-CoA mutase (MCM), the only AdoCbl-dependent enzyme in humans. Genetic defects in the switch III region of MMAA lead to the genetic disorder methylmalonic aciduria in which the body is unable to process certain lipids. Here, we present a crystal structure of Methylobacterium extorquens MeaB bound to a nonhydrolyzable guanosine triphosphate (GTP) analog guanosine-5'-[(β,γ)-methyleno]triphosphate (GMPPCP) with the Cbl-binding domain of its target mutase enzyme (MeMCM_cbl). This structure provides an explanation for the stimulation of the GTP hydrolyase activity of MeaB afforded by target

SUBMITTER: Vaccaro FA 

PROVIDER: S-EPMC9974510 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature