Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

EC-BLAST: a tool to automatically search and compare enzyme reactions

Nature Methods volume 11, pages 171–174 (2014)Cite this article

Subjects

Abstract

We present EC-BLAST (http://www.ebi.ac.uk/thornton-srv/software/rbl/), an algorithm and Web tool for quantitative similarity searches between enzyme reactions at three levels: bond change, reaction center and reaction structure similarity. It uses bond changes and reaction patterns for all known biochemical reactions derived from atom-atom mapping across each reaction. EC-BLAST has the potential to improve enzyme classification, identify previously uncharacterized or new biochemical transformations, improve the assignment of enzyme function to sequences, and assist in enzyme engineering.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2: All-by-all comparison across ∼6,000 mapped representative enzyme reactions in the EC-BLAST database (Supplementary Data 1).
Figure 3: Characterizing the universe of enzyme reactions using EC-BLAST.

Similar content being viewed by others

References

  1. Thompson, R.H.S. Science 137, 405–408 (1962).

    Article  CAS  Google Scholar 

  2. Tipton, K. & Boyce, S. Bioinformatics 16, 34–40 (2000).

    Article  CAS  Google Scholar 

  3. Yamanishi, Y., Hattori, M., Kotera, M., Goto, S. & Kanehisa, M. Bioinformatics 25, i179–i186 (2009).

    Article  CAS  Google Scholar 

  4. Gasteiger, J. Handbook of Chemoinformatics (Wiley, 2003).

  5. Chen, L. & Gasteiger, J. J. Am. Chem. Soc. 119, 4033–4042 (1997).

    Article  CAS  Google Scholar 

  6. Leber, M., Egelhofer, V., Schomburg, I. & Schomburg, D. Bioinformatics 25, 3135–3142 (2009).

    Article  CAS  Google Scholar 

  7. Faulon, J.-L., Misra, M., Martin, S., Sale, K. & Sapra, R. Bioinformatics 24, 225–233 (2008).

    Article  CAS  Google Scholar 

  8. Kotera, M., Okuno, Y., Hattori, M., Goto, S. & Kanehisa, M. J. Am. Chem. Soc. 126, 16487–16498 (2004).

    Article  CAS  Google Scholar 

  9. Egelhofer, V., Schomburg, I. & Schomburg, D. PLoS Comput. Biol. 6, e1000661 (2010).

    Article  Google Scholar 

  10. O'Boyle, N.M., Holliday, G.L., Almonacid, D.E. & Mitchell, J.B.O. J. Mol. Biol. 368, 1484–1499 (2007).

    Article  CAS  Google Scholar 

  11. Zhang, Q.-Y. & Aires-De-Sousa, J. J. Chem. Inf. Model. 45, 1775–1783 (2005).

    Article  CAS  Google Scholar 

  12. Latino, D.A.R.S.D. & Aires-de-Sousa, J.J. Angew. Chem. Int. Edn Engl. 45, 2066–2069 (2006).

    Article  CAS  Google Scholar 

  13. Mu, F., Unkefer, P.J., Unkefer, C.J. & Hlavacek, W.S. Bioinformatics 22, 3082–3088 (2006).

    Article  CAS  Google Scholar 

  14. Chen, W.L., Chen, D.Z. & Taylor, K.T. Wiley Interdiscip. Rev. Comput. Mol. Sci. 3, 560–593 (2013).

    Article  CAS  Google Scholar 

  15. Kanehisa, M., Goto, S., Sato, Y., Furumichi, M. & Tanabe, M. Nucleic Acids Res. 40, D109–D114 (2012).

    Article  CAS  Google Scholar 

  16. Rahman, S.A., Bashton, M., Holliday, G.L., Schrader, R. & Thornton, J.M. J. Cheminform. 1, 12 (2009).

    Article  Google Scholar 

  17. Jochum, C., Gasteiger, J. & Ugi, I. Angew. Chem. Int. Edn Engl. 19, 495–505 (1980).

    Article  Google Scholar 

  18. Ugi, I. et al. Angew. Chem. Int. Edn Engl. 18, 111–123 (1979).

    Article  Google Scholar 

  19. Steinbeck, C. et al. Curr. Pharm. Des. 12, 2111–2120 (2006).

    Article  CAS  Google Scholar 

  20. Sing, T., Sander, O., Beerenwinkel, N. & Lengauer, T. Bioinformatics 21, 3940–3941 (2005).

    Article  CAS  Google Scholar 

  21. Cuff, A.L. et al. Nucleic Acids Res. 39, D420–D426 (2011).

    Article  CAS  Google Scholar 

  22. Lees, J. et al. Nucleic Acids Res. 40, D465–D471 (2012).

    Article  CAS  Google Scholar 

  23. Theocharidis, A., van Dongen, S., Enright, A.J. & Freeman, T.C. Nat. Protoc. 4, 1535–1550 (2009).

    Article  CAS  Google Scholar 

  24. Dalby, A. et al. J. Chem. Inf. Model. 32, 244–255 (1992).

    Article  CAS  Google Scholar 

  25. Heller, S., McNaught, A., Stein, S., Tchekhovskoi, D. & Pletnev, I. J. Cheminform. 5, 7 (2013).

    Article  CAS  Google Scholar 

  26. Rahman, S.A., Advani, P., Schunk, R., Schrader, R. & Schomburg, D. Bioinformatics 21, 1189–1193 (2005).

    Article  CAS  Google Scholar 

  27. Rahman, S.A. Pathway Hunter Tool (PHT) – A Platform for Metabolic Network Analysis and Potential Drug Targeting. PhD thesis, Univ. Cologne (2007).

  28. Dugundji, J. & Ugi, I. in Computers in Chemistry 19–64 (Springer, 1973).

  29. Cahn, R.S., Ingold, C. & Prelog, V. Angew. Chem. Int. Edn Engl. 5, 385–415 (1966).

    Article  CAS  Google Scholar 

  30. Prelog, V. & Helmchen, G.N. Angew. Chem. Int. Edn Engl. 21, 567–583 (1982).

    Article  Google Scholar 

  31. Faulon, J.-L. & Bender, A. Handbook of Chemoinformatics Algorithms (Chapman and Hall/CRC, 2010).

  32. O'Boyle, N.M. et al. J. Cheminform. 3, 33 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

S.A.R., S.M.C. and G.L.H. acknowledge funding from the EMBL. N.F. and S.A.R. acknowledge funding from the Wellcome Trust (grant no. 081989/Z/07/A). We thank L. Baldacci, F. Fenninger, G. Torrance, S. Choudhary, N. Gopal, and S.T. Williams for their technical contributions. We thank D. Schomburg, J. Mitchell and C. Steinbeck for their support; the IUBMB-EC commission for their support and encouragement; J. May for improving the stereo detection library; and E. Willighagen and other Chemistry Development Kit (CDK) developers for helping out with the CDK library and timely review of the patches.

Author information

Author notes

  1. Nicholas Furnham & Gemma L Holliday

    Present address: Present addresses: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, London, UK (N.F.) Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA (G.L.H.).,

Authors and Affiliations

  1. European Molecular Biology Laboratory–European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, UK

    Syed Asad Rahman, Sergio Martinez Cuesta, Nicholas Furnham, Gemma L Holliday & Janet M Thornton

Authors
  1. Syed Asad Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sergio Martinez Cuesta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicholas Furnham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gemma L Holliday
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Janet M Thornton
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.A.R. developed the algorithm, code and the EC-BLAST tool. S.A.R. and J.M.T. wrote the majority of the manuscript and performed the statistical analysis. S.M.C. and G.L.H. were involved in curating the molecules, testing the chemical validity of the reaction similarity clusters and helping in the manuscript write up. S.A.R. and N.F. performed the analysis of the PPI family and the write-up. J.M.T. supervised the whole project and the manuscript write-up.

Corresponding authors

Correspondence to Syed Asad Rahman or Janet M Thornton.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Tables 1–3, Supplementary Results and Supplementary Notes 1 and 2 (PDF 6978 kb)

Supplementary Data 1

Source raw data for Figure 2 containing similarity scores between EC-Reactions, cluster information, etc. (ZIP 274328 kb)

Supplementary Data 2

Source data for Supplementary Figure 1 (XLSX 3489 kb)

Supplementary Data 3

Source data for Supplementary Figure 2 (XLSX 3489 kb)

Source data

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rahman, S., Cuesta, S., Furnham, N. et al. EC-BLAST: a tool to automatically search and compare enzyme reactions. Nat Methods 11, 171–174 (2014). https://doi.org/10.1038/nmeth.2803

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.2803

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing