Skip to main content
SpringerLink
Log in

Engineering sulfotransferases to modify heparan sulfate

  • Brief Communication
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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.

Similar content being viewed by others

Accession codes

Accessions

Protein Data Bank

References

  1. Liu, J. & Pedersen, L.C. Appl. Microbiol. Biotechnol. 74, 263–272 (2007).

    Article  CAS  Google Scholar 

  2. Gama, C. et al. Nat. Chem. Biol. 2, 467–473 (2006).

    Article  CAS  Google Scholar 

  3. Shriver, Z., Raguram, S. & Sasisekharan, R. Nat. Rev. Drug Discov. 3, 863–873 (2004).

    Article  CAS  Google Scholar 

  4. Chen, J., Jones, C.L. & Liu, J. Chem. Biol. 14, 986–993 (2007).

    Article  CAS  Google Scholar 

  5. Kuberan, B., Lech, M.Z., Beeler, D.L., Wu, Z.L. & Rosenberg, R.D. Nat. Biotechnol. 21, 1343–1346 (2003).

    Article  CAS  Google Scholar 

  6. Kakuta, Y., Pedersen, L.G., Carter, C.W., Negishi, M. & Pedersen, L.C. Nat. Struct. Biol. 4, 904–908 (1997).

    Article  CAS  Google Scholar 

  7. Kakuta, Y., Sueyoshi, T., Negishi, M. & Pedersen, L.C. J. Biol. Chem. 274, 10673–10676 (1999).

    Article  CAS  Google Scholar 

  8. Moon, A. et al. J. Biol. Chem. 279, 45185–45193 (2004).

    Article  CAS  Google Scholar 

  9. Mikhailov, D., Mayo, K.H., Pervin, A. & Linhardt, R.J. Biochem. J. 315, 447–454 (1996).

    Article  CAS  Google Scholar 

  10. Kraulis, P.J. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  11. Merrit, E.A. & Bacon, D.J. Methods Enzymol. 277, 505–524 (1997).

    Article  Google Scholar 

  12. DeLano, W.L. The PyMOL Molecular Graphics System (DeLano Scientific, San Carlos, California, 2002).

    Google Scholar 

Download references

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.

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea F Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danyin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars C Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.66

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation