Skip to main content
SpringerLink
Log in

Structure of a unique binuclear manganese cluster in arginase

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

EACH individual excretes roughly 10 kg of urea per year, as a result of the hydrolysis of arginine in the final cytosolic step of the urea cycle1. This reaction allows the disposal of nitrogenous waste from protein catabolism, and is catalysed by the liver arginase enzyme2. In other tissues that lack a complete urea cycle, arginase regulates cellular arginine and ornithine concentrations for biosynthetic reactions3, including nitric oxide synthesis: in the macrophage, arginase activity is reciprocally coordinated with that of NO synthase to modulate NO-dependent cytotoxicity4–9. The bioinorganic chemistry of arginase is particularly rich because this enzyme is one of very few that specifically requires a spin-coupled Mn2+ –Mn2+ cluster for catalytic activity in vitro and in vivo10. The 2.1 Å-resolution crystal structure of trimeric11 rat liver arginase reveals that this unique metal cluster resides at the bottom of an active-site cleft that is 15 Å deep. Analysis of the structure indicates that arginine hydrolysis is achieved by a metal-activated solvent molecule which symmetrically bridges the two Mn2+ ions.

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

Similar content being viewed by others

References

  1. Krebs, H. A. & Henseleit, K. Hoppe-Seyler's Z. Physiol. Chem. 210, 33–66 (1932).

    Article  CAS  Google Scholar 

  2. Herzfeld, A. & Raper, S. M. Biochem. J. 153, 469–478 (1976).

    Article  CAS  Google Scholar 

  3. Yip, M. C. M. & Knox, W. E. Biochem. J. 127, 893–899 (1972).

    Article  CAS  Google Scholar 

  4. Corraliza, I. M., Soler, G., Eichmann, K. & Modolell, M. Biochem. Biophys. Res. Commun. 206, 667–673 (1995).

    Article  CAS  Google Scholar 

  5. Daghigh, F., Fukuto, J. M. & Ash, D. E. Biochem. Biophys. Res. Commun. 202, 174–180 (1994).

    Article  CAS  Google Scholar 

  6. Chénais, B., Yapo, A., Lepoivre, M. & Tenu, J.-P. Biochem. Biophys. Res. Commun. 196, 1558–1565 (1993).

    Article  Google Scholar 

  7. Klatt, P., Schmidt, K., Uray, G. & Mayer, B. J. Biol. Chem. 268, 14781–14787 (1993).

    CAS  PubMed  Google Scholar 

  8. Keller, R., Gehri, R., Keist, R., Huf, E. & Kayser, F. H. Cell. Immunol. 134, 249–256 (1991).

    Article  CAS  Google Scholar 

  9. Albina, J. E., Henry, W. L., Mastrofrancesco, B., Martin, B.-A. & Reichner, J. S. J. Immunol. 155, 4391–4396 (1995).

    CAS  PubMed  Google Scholar 

  10. Reczkowski, R. S. & Ash, D. E. J. Am. Chem. Soc. 114, 10992–10994 (1992).

    Article  CAS  Google Scholar 

  11. Kanyo, Z. F., Chen, C.-Y., Daghigh, F., Ash, D. E. & Christianson, D. W. J. Mol. Biol. 224, 1175–1177 (1992).

    Article  CAS  Google Scholar 

  12. Christianson, D. W. & Alexander, R. S. J. Am. Chem. Soc. 111, 6412–6419 (1989).

    Article  CAS  Google Scholar 

  13. Rardin, R. L., Tolman, W. B. & Lippard, S. J. New J. Chem. 15, 417–430 (1991).

    CAS  Google Scholar 

  14. Cavalli, R. C., Burke, C. J., Kawamoto, S., Soprano, D. R. & Ash, D. E. Biochemistry 33, 10652–10657 (1994).

    Article  CAS  Google Scholar 

  15. Christianson, D. W. & Fierke, C. A. Acc. Chem. Res. 29, 331–339 (1996).

    Article  CAS  Google Scholar 

  16. Reczkowski, R. S. & Ash, D. E. Arch. Biochem. Biophys. 312, 31–37 (1994).

    Article  CAS  Google Scholar 

  17. Kuhn, N. J., Talbot, J. & Ward, S. Arch. Biochem. Biophys. 286, 217–221 (1991).

    Article  CAS  Google Scholar 

  18. Jabri, E., Carr, M. B., Hausinger, R. P. & Karplus, P. A. Science 268, 998–1004 (1995).

    Article  ADS  CAS  Google Scholar 

  19. Park, I.-S. & Hausinger, R. P. Biochemistry 35, 5345–5352 (1996).

    Article  CAS  Google Scholar 

  20. Nyborg, J. & Wonacott, A. J. in The Rotation Method in Crystallography (eds Arndt, U. W. & Wonacott, A. J.) 139–152 (North-Holland, Amsterdam, 1977).

    Google Scholar 

  21. Collaborative Computational Project No. 4 Acta Crystallogr. D 50, 760–763 (1994).

  22. Furey, W. & Swaminathan, S. Am. Crystallogr. Assoc. Mtg Prog. Abstr. 18, 73 (1990).

    Google Scholar 

  23. Brünger, A. T., Kuriyan, J. & Karplus, M. Science 235, 458–460 (1987).

    Article  ADS  Google Scholar 

  24. Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Acta. Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

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

    Article  Google Scholar 

  26. Bacon, D. J. & Anderson, W. F. J. Mol. Graph. 6, 219–220 (1988).

    Article  Google Scholar 

  27. Merritt, E. A. & Murphy, M. E. P. Acta Crystallogr. D 50, 869–873 (1994).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Pennsylvania, 231S. 34th Street, Philadelphia, Pennsylvania, 19104-6323, USA

    Zoltan F. Kanyo, Laura R. Scolnick & David W. Christianson

  2. Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania, 19140, USA

    David E. Ash

Authors
  1. Zoltan F. Kanyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura R. Scolnick
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David E. Ash
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David W. Christianson
    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

Kanyo, Z., Scolnick, L., Ash, D. et al. Structure of a unique binuclear manganese cluster in arginase. Nature 383, 554–557 (1996). https://doi.org/10.1038/383554a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/383554a0

  • Springer Nature Limited

This article is cited by

Search

Navigation