Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1.

ABSTRACT: During collagen biosynthesis, lysine residues undergo extensive post-translational modifications through the alternate action of two distinct metal ion-dependent enzyme families (i.e., LH/PLODs and GLT25D/COLGALT), ultimately producing the highly conserved α-(1,2)-glucosyl-β-(1,O)-galactosyl-5-hydroxylysine pattern. Malfunctions in these enzymes are linked to developmental pathologies and extracellular matrix alterations associated to enhanced aggressiveness of solid tumors. Here, we characterized human GLT25D1/COLGALT1, revealing an elongated head-to-head homodimeric assembly. Each monomer encompasses two domains (named GT1 and GT2), both unexpectedly capable of binding metal ion cofactors and UDP-α-galactose donor substrates, resulting in four candidate catalytic sites per dimer. We iden

SUBMITTER: De Marco M 

PROVIDER: S-EPMC12003778 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature