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J Biol Chem, Vol. 274, Issue 16, 10673-10676, April 16, 1999

COMMUNICATION
Crystal Structure of the Sulfotransferase Domain of Human Heparan Sulfate N-Deacetylase/ N-Sulfotransferase 1

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

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 alpha /beta fold with a central five-stranded parallel beta -sheet and a three-stranded anti-parallel beta -sheet bearing an interstrand disulfide bond. The structural regions alpha 1, alpha 6, beta 1, beta 7, 5'-phosphosulfate binding loop (between beta 1 and alpha 1), and a random coil (between beta 8 and alpha 13) constitute the PAP binding site of NST1. The alpha 6 and random coil (between beta 2 and alpha 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.


Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.



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