Downstream Products are Potent Inhibitors of the Heparan Sulfate 2-O-Sulfotransferase.

ABSTRACT: Heparan Sulfate (HS) is a cell signaling molecule linked to pathological processes ranging from cancer to viral entry, yet fundamental aspects of its biosynthesis remain incompletely understood. Here, the binding preferences of the uronyl 2-O-sulfotransferase (HS2ST) are examined with variably-sulfated hexasaccharides. Surprisingly, heavily sulfated oligosaccharides formed by later-acting sulfotransferases bind more tightly to HS2ST than those corresponding to its natural substrate or product. Inhibition assays also indicate that the IC₅₀ values correlate simply with degree of oligosaccharide sulfation. Structural analysis predicts a mode of inhibition in which 6-O-sulfate groups located on glucosamine residues present in highly-sulfated oligosaccharides occupy the canonical bin

SUBMITTER: Thieker DF 

PROVIDER: S-EPMC6081452 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature