Results: Reported here is the crystal structure at 2 Angstrom resolution of methylmalonyl-CoA mutase from Propionibacterium shermanii in complex with coenzyme B-12 and with the partial substrate desulpho-CoA (lacking the succinyl group and the sulphur atom of the substrate). The coenzyme is bound by a domain which shares a similar fold to those of flavodoxin and the B-12-binding domain of methylcobalamin-dependent methionine synthase. The cobalt atom is coordinated, via a long bond, to a histidine from the protein, The partial substrate is bound along the axis of a (beta/alpha)(B) TIM barrel domain.

Conclusions: The histidine-cobalt distance is very long (2.5 Angstrom compared with 1.95-2.2 Angstrom in free cobalamins), suggesting that the enzyme positions the histidine in order to weaken the metal-carbon bond of the cofactor and favour the formation of the initial radical species. The active site is deeply buried, and the only access to it is through a narrow tunnel along the axis of the TIM barrel domain.