title: "Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.
abstract: Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity.
authors.affiliation: Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; National Glycoengineering Research Center, Shandong University, Jinan 250012, China. Electronic address: fswang@sdu.edu.cn.
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address: shengjuzheng@sdu.edu.cn.
authors.forename: Juzheng
authors.initials: J
authors.lastname: Sheng
mesh_terms: D000818:Animals; D055162:Biocatalysis; D053898:Biosynthetic Pathways; D005944:Glucosamine / Q000737:chemistry; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000737:chemistry*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D015394:Molecular Structure; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D005944:Glucosamine; D006497:Heparan Sulfate; D007527:Isoenzymes; D015238:Sulfotransferases
keywords: Biosynthesis mechanism; C5-epimerase; Heparan sulfate; N-deacetylase/N-sulfotransferase; O-sulfotransferase