Heparan sulphate N-sulphotransferase activity: Reaction mechanism and substrate recognition

Y. Kakuta, L. Li, L. C. Pedersen, L. G. Pedersen, M. Negishi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Human heparan sulphate N-deacetylase/N-sulphotransferase 1 sulphates the NH3+ group of the glucosamine moiety of the heparan chain in heparan sulphate/heparin biosynthesis. An open cleft that runs perpendicular to the sulphate donor 3′-phosphoadenosine 5′-phosphosulphate may constitute the acceptor substrate-binding site of the sulphotransferase domain (hNST1) [Kakuta, Sueyoshi, Negishi and Pedersen (1999) J. Biol. Chem. 274, 10673-10676]. When a hexasaccharide model chain is docked into the active site, only a trisaccharide (-ldoA-GlcN-ldoA-) portion interacts directly with the cleft residues: Trp-713, His-716 and His-720 from α helix 6, and Phe-640, Glu-641, Glu-642, Gln-644 and ASh-647 from random coil (residues 640-647). Mutation of these residues either abolishes or greatly reduces hNST1 activity. Glu-642 may play the critical role of catalytic base in the sulphuryl group transfer reaction, as indicated by its hydrogen-bonding distance to the NH3+ group of the glucosamine moiety in the model and by mutational data.

Original languageEnglish
Pages (from-to)331-334
Number of pages4
JournalBiochemical Society Transactions
Volume31
Issue number2
DOIs
Publication statusPublished - Apr 1 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry

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