Crystal Structure of the Sulfotransferase Domain of Human Heparan Sulfate N-Deacetylase/ N-Sulfotransferase 1*
- From the Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709
Abstract
Heparan sulfateN-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.
Footnotes
-
↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The atomic coordinates and structure factors (code 1NST) has been deposited in the Protein Data Bank, Brookhaven National Laboratory, Upton, NY.
-
↵‡ JSPS Research Fellow at National Institutes of Health.
-
↵§ To whom correspondence should be addressed: Head, Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Tel.: 919-541-2404; Fax: 919-541-0696; E-mail: negishi{at}niehs.nih.gov.
- Abbreviations:
- PAPS
-
3′-phosphoadenosine 5′-phosphosulfate
- PAP
-
3′-phosphoadenosine 5′-phosphate
- PSB-loop
-
5′-phosphosulfate binding loop
- 5′PSB
-
5′-phosphosulfate binding motif
- 3′PB
-
3′-phosphate binding motif
- NST1
-
the sulfotransferase domain of heparan sulfate N-deacetylase/N-sulfotransferase
- EST
-
estrogen sulfotransferase
-
- Received November 19, 1998.
- Revision received February 8, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
