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.

  • Letter
  • Published:

Doughnut-shaped structure of a bacterial muramidase revealed by X-ray crystallography

Nature volume 367, pages 750–753 (1994)Cite this article

Abstract

THE integrity of the bacterial cell wall depends on the balanced action of several peptidoglycan (murein) synthesizing and degrading enzymes1,2. Penicillin inhibits the enzymes responsible for pep-tide crosslinks in the peptidoglycan polymer3. Enzymes that act solely on the glycosidic bonds are insensitive to this antibiotic, thus offering a target for the design of antibiotics distinct from the β-lactams. Here we report the X-ray structure of the periplasmic soluble lytic transglycosylase (SLT; Mr 70,000) from Escherichia coli This unique bacterial exomuramidase cleaves the β-l,4-glycosidic bonds of peptidoglycan to produce small 1,6-anhydro-muropeptides4–6. The structure of SLT reveals a 'superhelicaP ring of α-helices with a separate domain on top which resembles the fold of lysozyme. Site-directed mutagenesis and a crystallographic inhibitor-binding study confirmed that the lysozyme-like domain contains the active site of SLT.

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

Similar content being viewed by others

References

  1. Rogers, H. J., Perkins, H. R. & Ward, J. B. in Microbial Cell Walls and Membranes (eds Perkins, H. R. et al.) 437–460 (Chapman & Hall, London, 1980).

    Google Scholar 

  2. Höltje, J.-V. & Schwarz, U. in Molecular Cytology of Escherichia coli (ed. Nanninga, N.) 77–119 (Academic, London, 1985).

    Google Scholar 

  3. Waxman, D. J. & Strominger, J. L. A. Rev. Biochem. 52, 825–869 (1983).

    Article  CAS  Google Scholar 

  4. Höltje, J.-V., Mirelman, D., Sharon, N. & Schwarz, U. J. Bact. 124, 1067–1076 (1975).

    PubMed  Google Scholar 

  5. Keck, W., Wientjes, F. B. & Schwarz, U. Eur. J. Biochem. 148, 493–497 (1985).

    Article  CAS  Google Scholar 

  6. Engel, H., Kazemier, B. & Keck, W. J. Bact. 173, 6773–6782 (1991).

    Article  CAS  Google Scholar 

  7. Presnell, S. R. & Cohen, F. E. Proc. natn. Acad. Sci. U.S.A. 86, 6592–6595 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Banaszak, L., Sharrock, W. & Timmins, P. A. Rev. Biophys. biophys. Chem. 20, 221–246 (1991).

    Article  CAS  Google Scholar 

  9. Barlow, D. J. & Thornton, J. M. J. molec. Biol. 201, 601–619 (1988).

    Article  CAS  Google Scholar 

  10. Verschueren, K. H. G., Franken, S. M., Rozeboom, H. J., Kalk, K. H. & Dijkstra, B. W. J. molec. Biol. 232, 856–872 (1993).

    Article  CAS  Google Scholar 

  11. Imoto, T., Johnson, L. N., North, A. C. T., Phillips, D. C. & Rupley, J. A. in The Enzymes (ed. Boyer, P. D.) 666–868 (Academic, New York, 1972).

    Google Scholar 

  12. Weaver, L. H. & Matthews, B. W. J. molec. Biol. 193, 189–199 (1987).

    Article  CAS  Google Scholar 

  13. Blake, C. C. F. et al. Proc. R. Soc. Lond. B167, 378–388 (1967).

    ADS  CAS  PubMed  Google Scholar 

  14. Hardy, L. W. & Poteete, A. R. Biochemistry 30, 9457–9463 (1991).

    Article  CAS  Google Scholar 

  15. Strynadka, N. C. J. & James, M. N. G. J. molec. Biol. 220, 440–424 (1991).

    Article  Google Scholar 

  16. Beachey, E. H., Keck, W., de Pedro, M. A. & Schwarz, U. Eur. J. Biochem. 116, 355–358 (1981).

    Article  CAS  Google Scholar 

  17. Rozeboom, H. J., Dijkstra, B. W., Engel, H. & Keck, W. J. molec. Biol. 212, 557–559 (1990).

    Article  CAS  Google Scholar 

  18. Messerschmidt, A. & Pflugrath, J. W. J. appl. Crystallogr. 20, 306–315 (1987).

    Article  CAS  Google Scholar 

  19. Kabsch, W. J. appl. Crystallogr. 21, 916–924 (1988).

    Article  CAS  Google Scholar 

  20. Bricogne, G. Acta crystallogr. A 32, 832–847 (1976).

    Article  ADS  Google Scholar 

  21. Jones, T. A. J. appl. Crystallogr. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  22. Jones, T. A., Zou, J.-Y., Cowan, S. W. & Kjeldgaard, M. Acta crystallogr. A47, 110–119 (1991).

    Article  Google Scholar 

  23. Brünger, A. T. X-PLOR (Version 3.0) Manual (Yale Univ., New Haven, 1992).

    Google Scholar 

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

    Article  Google Scholar 

  25. Rossmann, M. G. & Argos, P. J. molec. Biol. 105, 75–96 (1976).

    Article  CAS  Google Scholar 

  26. Bernstein, F. C. et al. J. molec. Biol. 112, 535–542 (1977).

    Article  CAS  Google Scholar 

  27. Shinagawa, S., Maki, M., Kintaka, K., Imada, A. & Asai, M. J. Antibiot. 38, 17–23 (1985).

    Article  CAS  Google Scholar 

  28. Templin, M. F., Edwards, D. H. & Höltje, J.-V. J. biol. Chem. 267, 20039–20043 (1992).

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Henk Engel

    Present address: Department of Clinical Chemistry, University Hospital Rotterdam-Dijkzigt, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

  2. Bauke W. Dijkstra: To whom correspondence should be addressed.

Authors and Affiliations

  1. BIOSON Research Institute, Department of Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

    Andy-Mark W. H. Thunnissen, Kor H. Kalk, Henriëtte J Rozeboom, Henk Engel & Bauke W. Dijkstra

  2. Pharma Research Department, F. Hoffmann-La Roche Ltd, CH-4002, Basel, Switzerland

    Arnoud J. Dijkstra & Wolfgang Keck

Authors
  1. Andy-Mark W. H. Thunnissen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arnoud J. Dijkstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kor H. Kalk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henriëtte J Rozeboom
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henk Engel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wolfgang Keck
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bauke W. Dijkstra
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thunnissen, AM., Dijkstra, A., Kalk, K. et al. Doughnut-shaped structure of a bacterial muramidase revealed by X-ray crystallography. Nature 367, 750–753 (1994). https://doi.org/10.1038/367750a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/367750a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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