A Single Protein Catalyzes Both N-Deacetylation and N-Sulfation During the Biosynthesis of Heparan Sulfate

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 9; pp. 3885 - 3888
• Main Authors: Wei, Zheng, Swiedler, Stuart J., Ishihara, Masayuki, Orellana, Ariel, Hirschberg, Carlos B.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.05.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Acetylglucosamine - metabolism; Amidohydrolases - genetics; Amidohydrolases - isolation & purification; Amidohydrolases - metabolism; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Biochemistry; Biological and medical sciences; Biosynthesis; Carbohydrates; Cell Line; Cell Membrane - enzymology; COS cells; Cytosol - enzymology; Electrophoresis, Polyacrylamide Gel; Enzymes; Fundamental and applied biological sciences. Psychology; heparan sulfate; heparan sulfate N-deacetylase; heparan sulfate N-sulfotransferase; Heparin; Heparitin Sulfate - biosynthesis; Holosides; Kinetics; Liver; Liver - enzymology; Mast cells; Molecular Sequence Data; Molecular Weight; Oligodeoxyribonucleotides; Other biological molecules; Plasmids; Polymers; Proteins; Rats; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; Rodents; Sulfates; Sulfotransferases - genetics; Sulfotransferases - isolation & purification; Sulfotransferases - metabolism; Transfection; use; Rat; Liver; Rodentia; Glycan; Golgi apparatus; Sulfatation; Vertebrata; Mammalia; Enzymatic activity; Deacetylation; Heparitin sulfate; Recombinant protein; Polysaccharide
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.9.3885

Heparan sulfate is a highly sulfated carbohydrate polymer that binds to and modulates the activities of numerous proteins. The formation of these protein-binding domains in heparan sulfate is dependent on a series of biosynthetic reactions that modify the polysaccharide backbone; the initiating and rate-limiting steps of this process are the N-deacetylation and N-sulfation of N-acetylglucosamine residues in the polymer. We now report that in the rat liver, biosynthesis of heparan sulfate utilizes a single protein that possesses both N-deacetylase and N-sulfotransferase activities. This was accomplished by demonstrating that both activities resided in a purified soluble fusion protein containing the Golgi-lumenal portion of the enzyme. We propose that this protein be renamed the rat liver Golgi heparan sulfate N-deacetylase/N-sulfotransferase.