A SINGLE PROTEIN CATALYZES BOTH N-DEACETYLATION AND N-SULFATION DURING THE BIOSYNTHESIS OF HEPARAN-SULFATE

Heparan sulfate is a highly sulfated carbohydrate polymer that binds t o and modulates the activities of numerous proteins. The formation of these protein-binding domains in heparan sulfate is dependent on a ser ies of biosynthetic reactions that modify the polysaccharide backbone; the initiating and rate-limiting steps of this process are the N-deac etylation and N-sulfation of N-acetylglucosamine residues in the polym er. We now report that in the rat liver, biosynthesis of heparan sulfa te utilizes a single protein that possesses both N-deacetylase and N-s ulfotransferase activities. This was accomplished by demonstrating tha t both activities resided in a purified soluble fusion protein contain ing the Golgi-lumenal portion of the enzyme. We propose that this prot ein be renamed the rat liver Golgi heparan sulfate N-deacetylase/N-sul fotransferase.