Structural basis of the dominant inheritance of hypermethioninemia associated with the Arg264His mutation in the MAT1A gene.

ABSTRACT: Methionine adenosyltransferase (MAT) deficiency, characterized by isolated persistent hypermethioninemia (IPH), is caused by mutations in the MAT1A gene encoding MATαl, one of the major hepatic enzymes. Most of the associated hypermethioninemic conditions are inherited as autosomal recessive traits; however, dominant inheritance of hypermethioninemia is caused by an Arg264His (R264H) mutation. This mutation has been confirmed in a screening programme of newborns as the most common mutation in babies with IPH. Arg264 makes an inter-subunit salt bridge located at the dimer interface where the active site assembles. Here, it is demonstrated that the R264H mutation results in greatly reduced MAT activity, while retaining its ability to dimerize, indicating that the lower activity arises from a

SUBMITTER: Panmanee J 

PROVIDER: S-EPMC7271947 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature