Affinity, kinetic and structural study of the interaction of 3-O-sulfotransferase isoform 1 with heparan sulfate

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Authors
Munoz, Eva
Xu, Ding
Kemp, Melissa
Zhang, Fuming
Liu, Jian
Linhardt, Robert J.
Issue Date
2006-04-25
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
The 3-O-sulfonation of glucosamine residues in heparan sulfate (HS) by 3-O-sulfotransferase (3-OST) is a key substitution that is present in HS sequences of biological importance, in particular HS anticoagulant activity. Six different isoforms of 3-OST have been identified that exhibit different substrate specificity. In this paper the affinity and kinetics of the interaction between 3-O-sulfotransferase isoform 1 (3-OST-1) and HS have been examined using surface plasmon resonance (SPR). 3-OST-1 binds with micomolar affinity to HS (KD = 2.79 μM), and this interaction is apparently independent of the presence of the coenzyme, 3‘-phosphoadenosine 5‘-phosphosulfate (PAPS). A conformational change in the complex has also been detected, supporting data from previous studies. Selected 3-OST-1 mutants have provided valuable information of amino acid residues that participate in 3-OST-1 interaction with HS substrate and its catalytic activity. The results from this study contribute to understanding the substrate specificity among the 3-OST isoforms and in the mechanism of 3-OST-1-catalyzed biosynthesis of anticoagulant HS.
Description
Biochemistry, 45, 5122-5118
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Full Citation
Affinity, kinetic and structural study of the interaction of 3-O-sulfotransferase isoform 1 with heparan sulfate, E. Mu“oz, D. Xu, J. Liu, R. J. Linhardt, Biochemistry, 45, 5122-5118, 2006.
Publisher
American Chemical Society (ACS)
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DOI
ISSN
62960
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