Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.

ABSTRACT: Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 Å resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore

SUBMITTER: McCorvie TJ 

PROVIDER: S-EPMC5081055 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature