biostudies-literatureVaccaro FAHHS | National Institutes of HealthHoward Hughes Medical InstituteNIGMS NIH HHSe2214085120https://www.ebi.ac.uk/biostudies/studies/S-EPMC9974510biostudies-literatureUnknown120(8)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 <i>Methylobacterium extorquens</i> 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 (<i>Me</i>MCM_cbl). This structure provides an explanation for the stimulation of the GTP hydrolyase activity of MeaB afforded by targetProceedings of the National Academy of Sciences of the United States of AmericaStructure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery.PMC9974510T31 GM008313R35 GM126982F31 GM131648T32 GM008313InvestigatorBorn DADrennan CLVaccaro FAfalseStructure of metallochaperone in complex with the cobalamin-binding domain of its target mutase provides insight into cofactor delivery.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 <i>Methylobacterium extorquens</i> 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 (<i>Me</i>MCM_cbl). This structure provides an explanation for the stimulation of the GTP hydrolyase activity of MeaB afforded by target2023-01-01T00:00:00Z2023 Feb2026-05-28T08:07:58.176Z2025-04-25T17:08:27.32ZS-EPMC99745103678736010.1073/pnas.2214085120