Document Detail

Heparan sulfate biosynthesis: a theoretical study of the initial sulfation step by N-deacetylase/N-sulfotransferase.
MedLine Citation:
PMID:  11106599     Owner:  NLM     Status:  MEDLINE    
Heparan sulfate N-deacetylase/N-sulfotransferase (NDST) catalyzes the deacetylation and sulfation of N-acetyl-D-glucosamine residues of heparan sulfate, a key step in its biosynthesis. Recent crystallographic and mutational studies have identified several potentially catalytic residues of the sulfotransferase domain of this enzyme (, J. Biol. Chem. 274:10673-10676). We have used the x-ray crystal structure of heparan sulfate N-sulfotransferase with 3'-phosphoadenosine 5'-phosphate to build a solution model with cofactor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and a model heparan sulfate ligand bound, and subsequently performed a 2-ns dynamics solution simulation. The simulation results confirm the importance of residues Glu(642), Lys(614), and Lys(833), with the possible involvement of Thr(617) and Thr(618), in binding PAPS. Additionally, Lys(676) is found in close proximity to the reaction site in our solvated structure. This study illustrates for the first time the possible involvement of water in the catalysis. Three water molecules were found in the binding site, where they are coordinated to PAPS, heparan sulfate, and the catalytic residues.
A Gorokhov; L Perera; T A Darden; M Negishi; L C Pedersen; L G Pedersen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biophysical journal     Volume:  79     ISSN:  0006-3495     ISO Abbreviation:  Biophys. J.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-18     Completed Date:  2001-01-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2909-17     Citation Subset:  IM    
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
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MeSH Terms
Amidohydrolases / chemistry*,  metabolism*
Amino Acid Sequence
Catalytic Domain
Crystallography, X-Ray
Glutamic Acid
Heparitin Sulfate / biosynthesis*
Molecular Sequence Data
Sequence Alignment
Sequence Homology, Amino Acid
Sulfotransferases / chemistry*,  metabolism*
Grant Support
Reg. No./Substance:
56-86-0/Glutamic Acid; 56-87-1/Lysine; 72-19-5/Threonine; 9050-30-0/Heparitin Sulfate; EC 2.8.2.-/Sulfotransferases; EC sulfotransferase; EC 3.5.-/Amidohydrolases

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