Coenzyme B12-dependent-methylmalonyl coenzyme A (CoA) mutase (MCM) family, Beta subunit-like subfamily; contains bacterial proteins similar to the beta subunit of MCMs from Propionbacterium shermanni and Streptomyces cinnamonensis, which are alpha/beta heterodimers. For P. shermanni MCM, it is known that only the alpha subunit binds coenzyme B12 and substrates. The role of the beta subunit is unclear. MCM catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. The reaction proceeds via radical intermediates beginning with a substrate-induced homolytic cleavage of the Co-C bond of coenzyme B12 to produce cob(II)alamin and the deoxyadenosyl radical. MCM plays an important role in the conversion of propionyl-CoA to succinyl-CoA during the degradation of propionate for the Krebs cycle. Methylobacterium extorquens MCM participates in the glyoxylate regeneration pathway. In M. extorquens, MCM forms a complex with MeaB; MeaB may protect MCM from irreversible inactivation. In some bacteria, MCM is involved in the reverse metabolic reaction, the rearrangement of succinyl-CoA to methylmalonyl-CoA. Examples include P. shermanni MCM during propionic acid fermentation and Streptomyces MCM in polyketide biosynthesis.
Feature 1:substrate interaction site [chemical binding site]
Evidence:
Structure:7REQ_CD; P. shermanii MCM bound with 2-carboxypropyl-CoA inhibitor (methylmalonyl-CoA analogue); contacts at 3.5A
Structure:6REQ_AB; P. shermanii MCM bound with 3-carboxypropyl-CoA inhibitor (succinyl-CoA analog); contacts at 3.5A
Comment:The beta subunit of P. shermanni MCM contributes a single residue in the interaction with the substrate. This contributes to the resulting buried active site (or closed conformation) upon substrate binding. The substrate in the reaction is methylmalonyl coenzyme A. In some cases, MCM catalyzes the reverse reaction and the product, succinyl CoA, becomes the substrate.
Jiyao W et al.(2023). "The conserved domain database in 2023.",