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J Biol Chem, Vol. 274, Issue 16, 10673-10676, April 16, 1999
From the Pharmacogenetics Section, Laboratory of Reproductive and
Developmental Toxicology, NIEHS, National Institutes of Health,
Research Triangle Park, North Carolina 27709
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
/
fold with a central five-stranded parallel
-sheet and a
three-stranded anti-parallel
-sheet bearing an interstrand disulfide
bond. The structural regions
1,
6,
1,
7, 5'-phosphosulfate binding loop (between
1 and
1), and a random coil (between
8 and
13) constitute the PAP binding site of NST1. The
6 and random coil (between
2 and
2), 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.
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