Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.

ABSTRACT: Methylmalonyl-CoA mutase (MUT) is an essential enzyme in propionate catabolism that requires adenosylcobalamin as a cofactor. Almost 250 inherited mutations in the MUT gene are known to cause the devastating disorder methylmalonic aciduria; however, the mechanism of dysfunction of these mutations, more than half of which are missense changes, has not been thoroughly investigated. Here, we examined 23 patient missense mutations covering a spectrum of exonic/structural regions, clinical phenotypes, and ethnic populations in order to determine their influence on protein stability, using two recombinant expression systems and a thermostability assay, and enzymatic function by measuring MUT activity and affinity for its cofactor and substrate. Our data stratify MUT missense mutations into categ

SUBMITTER: Forny P 

PROVIDER: S-EPMC4441004 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature