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Engineering sulfotransferases to modify heparan sulfate

Nature Chemical Biology volume 4, pages 200–202 (2008)Cite this article

Abstract

The biosynthesis of heparan sulfate (HS) involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations of these residues altered the substrate specificities. Our results demonstrate the feasibility of tailoring the specificity of sulfotransferases to modify HS with desired functions.

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Figure 1: The substrate specificity of 3-OST isoforms and the biological functions of the HS modified by different 3-OST isoforms.
Figure 2: Structural characterization of 3-O-sulfotransferase isoforms 1, 3 and 5.

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Acknowledgements

The authors thank G. Cohen and R. Eisenberg (University of Pennsylvania) for providing gD-1 (306t) and anti-gD antibody. We also thank H. Kohn, L.G. Pedersen and T. Hall for reviewing the manuscript. This work is supported in part by a US National Institutes of Health grant (AI50050 to J.L.) and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (to L.C.P.). D.X. is a recipient of a predoctoral fellowship from the American Heart Association, MidAtlantic Affiliate.

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Authors and Affiliations

  1. Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.,

    Ding Xu, Danyin Song & Jian Liu

  2. Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, 27709, North Carolina, USA

    Andrea F Moon & Lars C Pedersen

Authors
  1. Ding Xu
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  2. Andrea F Moon
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  3. Danyin Song
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  4. Lars C Pedersen
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  5. Jian Liu
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Contributions

D.X., D.S. and J.L. prepared and characterized 3-OST mutants. A.F.M. and L.C.P. performed crystallization of 3-OST-5 and subsequent data analysis. D.X., A.F.M., L.C.P. and J.L. wrote the manuscript.

Corresponding author

Correspondence to Jian Liu.

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Supplementary Figures 1–4, Supplementary Tables 1–5 and Supplementary Methods (PDF 859 kb)

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Xu, D., Moon, A., Song, D. et al. Engineering sulfotransferases to modify heparan sulfate. Nat Chem Biol 4, 200–202 (2008). https://doi.org/10.1038/nchembio.66

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