Substrate binding mode and catalytic mechanism of human heparan sulfate d-glucuronyl C5 epimerase.

ABSTRACT: Heparan sulfate (HS) is a linear, complex polysaccharide that modulates the biological activities of proteins through binding sites made by a series of Golgi-localized enzymes. Of these, glucuronyl C5-epimerase (Glce) catalyzes C5-epimerization of the HS component, d-glucuronic acid (GlcA), into l-iduronic acid (IdoA), which provides internal flexibility to the polymer and forges protein-binding sites to ensure polymer function. Here we report crystal structures of human Glce in the unbound state and of an inactive mutant, as assessed by real-time NMR spectroscopy, bound with a (GlcA-GlcNS)_n substrate or a (IdoA-GlcNS)_n product. Deep infiltration of the oligosaccharides into the active site cleft imposes a sharp kink within the central GlcNS-GlcA/IdoA-GlcNS trisacchar

SUBMITTER: Debarnot C 

PROVIDER: S-EPMC6452739 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature