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:

Novel NADPH-binding domain revealed by the crystal structure of aldose reductase

Nature volume 355, pages 469–472 (1992)Cite this article

Abstract

ALDOSE reductase is the first enzyme in the polyol pathway and catalyses the NADPH-dependent reduction of D-glucose to D-sorbitol. Under normal physiological conditions aldose reductase participates in osmoregulation1, but under hyperglycaemic conditions it contributes to the onset and development of severe complications in diabetes2. Here we present the crystal structure of pig lens aldose reductase refined to an R-factor of 0.232 at 2.5-Å resolution. It exhibits a single domain folded in an eight-stranded parallel α/β barrel, similar to that in triose phosphate isomerase3 and a score of other enzymes. Hence, aldose reductase does not possess the expected canonical dinucleotide-binding domain4. Crystallographic analysis of the binding of 2′-monophospho-adenosine-5′-diphosphoribose, which competitively inhibits NADPH binding reveals that it binds into a cleft located at the C-terminal end of the strands of the α/β barrel. This represents a new type of binding for nicotinamide adenine dinucleotide coenzymes.

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. Burg, M. B. Kidney Int. 33, 635–641 (1988).

    Article  CAS  Google Scholar 

  2. Dvornik, D. in Aldose Reductase Inhibition. An Approach to the Prevention of Diabetic Complications (McGraw-Hill, New York, 1987).

    Google Scholar 

  3. Banner, D. W. et al. Nature 255, 609–614 (1975).

    Article  ADS  CAS  Google Scholar 

  4. Rossmann, M. G., Moras, D. & Olsen, K. W. Nature 250, 194–199 (1974).

    Article  ADS  CAS  Google Scholar 

  5. Wermuth, B. Prog. Clin. biol. Res. 174, 209–230 (1985).

    CAS  PubMed  Google Scholar 

  6. Bohren, K. M., Bullock, B., Wermuth, B. & Gabbay, K. H. J. biol. Chem 264, 9547–9551 (1989).

    CAS  PubMed  Google Scholar 

  7. Chung, S. & LaMendola, J. J. biol. Chem. 264, 14775–14777 (1989).

    CAS  PubMed  Google Scholar 

  8. Nishimura, C., Wistow, G. & Carper, D. Prog. clin. biol. Res. 290, 211–220 (1989).

    CAS  PubMed  Google Scholar 

  9. Schade, S. Z. et al. J. biol. Chem. 265, 3628–3635 (1990).

    CAS  PubMed  Google Scholar 

  10. Watanabe, K. et al. Proc. natn. Acad. Sci. U.S.A. 85, 11–15 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Anderson, S. et al. Science 230, 144–149 (1985).

    Article  ADS  CAS  Google Scholar 

  12. Fujii, Y. et al. J. biol. Chem. 265, 9914–9923 (1990).

    CAS  PubMed  Google Scholar 

  13. Winters, C. J., Molowa, D. T. & Guzelian, P. S. Biochemistry 29, 1080–1087 (1990).

    Article  CAS  Google Scholar 

  14. Oechsner, U., Magdolen, V. & Bandlow, W. FEBS Lett. 238, 123–128 (1988).

    Article  CAS  Google Scholar 

  15. Wierenga, R. K., Drenth, J. & Schulz, G. E. J. molec. Biol. 167, 725–739 (1983).

    Article  CAS  Google Scholar 

  16. Bystroff, C., Oatley, S. J. & Kraut, J. Biochemistry 29, 3263–3277 (1990).

    Article  CAS  Google Scholar 

  17. Wierenga, R. K., De Maeyer, M. C. H. & Hol, W. G. J. Biochemistry 24, 1346–1357 (1985).

    Article  CAS  Google Scholar 

  18. Farber, G. K. & Petsko, G. A. Trends biol. Sci. 15, 228–234 (1990).

    Article  CAS  Google Scholar 

  19. Lindqvist, Y., Brändén, C.-l., Mathews, F. S. & Lederer, F. J. biol. Chem. 266, 3198–3207 (1991).

    CAS  PubMed  Google Scholar 

  20. Rondeau, J. M. et al. J. molec. Biol. 195, 945–948 (1987).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Terwilliger, T. C. & Kim, S.-H. Acta crystallogr. A43, 1–5 (1987).

    Article  Google Scholar 

  23. Terwilliger, T. C. & Eisenberg, D. Acta crystallogr. A39, 813–817 (1983).

    Article  Google Scholar 

  24. Jones, T. A. in Computational Crystallography 303–317 (Clarendon, Oxford, 1982).

    Google Scholar 

  25. Brünger, A. T., Kuriyan, J. & Karplus, M. Science 35, 458–460 (1987).

    Article  ADS  Google Scholar 

  26. Priestle, J. J. appl. Crystallogr. 21, 572–576 (1988).

    Article  Google Scholar 

  27. Grimshaw, C. E. et al. Biochemistry 28, 5343–5353 (1989).

    Article  CAS  Google Scholar 

  28. Vander Jagt, D. L., Robinson, B., Taylor, K. K. & Hunsaker, L. A. J. biol. Chem. 265, 20982–20987 (1990).

    CAS  PubMed  Google Scholar 

  29. Del Corso, A. et al. Arch. biochem. biophys. 270, 604–610 (1989).

    Article  CAS  Google Scholar 

  30. Del Corso, A. et al. Arch. biochem. biophys. 283, 512–518 (1990).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. D. Moras: To whom correspondence should be addressed.

Authors and Affiliations

  1. Laboratoire de Cristallographie Biologique, Institut de Biologie Moleculaire et Cellulaire du CNRS, 15 rue R. Descartes, 67084, Strasbourg Cedex, France

    J.-M. Rondeau, F. Tête-Favier, A Podjarny & D. Moras

  2. Biostructure SA, Les Algorithmes, Batiment Euclide, Pare d'lnnovation, 67400, Illkirch-Graffenstaden, France

    J.-M. Rondeau & F. Tête-Favier

  3. Laboratoire de Chimie OrganiqueBiologique, Institut de Chimie, Universite Louis Pasteur, 4 rue B. Pascal, 67008, Strasbourg Cedex, France

    J.-M. Reymann, P. Barth & J.-F. Biellmann

Authors
  1. J.-M. Rondeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Tête-Favier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Podjarny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J.-M. Reymann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Barth
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J.-F. Biellmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. Moras
    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

Rondeau, JM., Tête-Favier, F., Podjarny, A. et al. Novel NADPH-binding domain revealed by the crystal structure of aldose reductase. Nature 355, 469–472 (1992). https://doi.org/10.1038/355469a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/355469a0

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