Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1

Yoshimitsu Kakuta, Tatsuya Sueyoshi, Masahiko Negishi, Lars C. Pedersen

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Abstract

Heparan sulfate N-deacetylase/N-sulfotransferase (HSNST) catalyzes the first and obligatory step in the biosynthesis of heparan sulfates and heparin. The crystal structure of the sulfotransferase domain (NST1) of human HSNST-1 has been determined at 2.3-Å resolution in a binary complex with 3'- phosphoadenosine 5'-phosphate (PAP). NST1 is approximately spherical with an open cleft, and consists of a single α/β fold with a central five-stranded parallel β-sheet and a three-stranded anti-parallel β-sheet bearing an interstrand disulfide bond. The structural regions α1, α6, β1, β7, 5'- phosphosulfate binding loop (between β1 and α1), and a random coil (between β8 and α13) constitute the PAP binding site of NST1. The α6 and random coil (between β2 and α2), which form an open cleft near the 5'-phosphate of the PAP molecule, may provide interactions for substrate binding. The conserved residue Lys-614 is in position to form a hydrogen bond with the bridge oxygen of the 5'-phosphate.

Original languageEnglish
Pages (from-to)10673-10676
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number16
DOIs
Publication statusPublished - Apr 16 1999

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Sulfotransferases
Crystal structure
Phosphates
Bearings (structural)
Heparitin Sulfate
Biosynthesis
Disulfides
Heparin
Hydrogen
Hydrogen bonds
Binding Sites
Oxygen
Molecules
heparitin sulfotransferase
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry

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Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1. / Kakuta, Yoshimitsu; Sueyoshi, Tatsuya; Negishi, Masahiko; Pedersen, Lars C.

In: Journal of Biological Chemistry, Vol. 274, No. 16, 16.04.1999, p. 10673-10676.

Research output: Contribution to journalArticle

Kakuta, Yoshimitsu ; Sueyoshi, Tatsuya ; Negishi, Masahiko ; Pedersen, Lars C. / Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/N-sulfotransferase 1. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 16. pp. 10673-10676.
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