[A molecular study of methylmalonic aciduria: structure-function correlations]

Cobalamin (Vitamin B12) non-responsive methylmalonic acidemia is caused by mutations in the MUT locus on chromosome 6p21 encoding the enzyme methylmalonyl CoA mutase (EC 5.4.99.2). This disorder has been extensively studied by biochemical, somatic cell genetic and molecular techniques. Mutations have been identified which cause classic mut(o) phenotypes in which there is no detectable enzymatic activity, as well as mut- phenotypes in which there is residual cobalamin-dependent activity. Mutations which exhibit interallelic complementation have been identified within both of these groups. These mutations illustrate the position, structure, and function of critical domains within this cobalamin binding enzyme and provide new insights into the biochemical and clinical consequences of enzyme deficiency. The homology of the cobalamin binding region has allowed mutations of the mutase to be mapped onto the x-ray structure of methionine synthase (EC 2.1.1.13).