IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v462y2009i7273d10.1038_nature08615.html
   My bibliography  Save this article

Hidden alternative structures of proline isomerase essential for catalysis

Author

Listed:
  • James S. Fraser

    (University of California, Berkeley, California 94720-3220, USA)

  • Michael W. Clarkson

    (Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA)

  • Sheena C. Degnan

    (University of California, Berkeley, California 94720-3220, USA)

  • Renske Erion

    (University of California, Berkeley, California 94720-3220, USA)

  • Dorothee Kern

    (Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA)

  • Tom Alber

    (University of California, Berkeley, California 94720-3220, USA)

Abstract

Altered states: in search of 'hidden' protein structures X-ray crystallography and NMR spectroscopy are two powerful tools used by structural biologists to determine the three-dimensional structures and characterize the dynamic properties of proteins. In this paper, the authors used both of these methods to identify and characterize a 'hidden' high-energy substate of human cyclophilin A, a proline isomerase. This was made possible by engineering a modified form of the enzyme incorporating a mutation at a distance from the active site that could stabilize this previously hidden conformation by inverting the equilibrium between the various substates and reducing the conformational interconversion rates and the catalytic rate. This approach should be broadly applicable to many other proteins and could lead to the reinterpretation of crystal structures determined previously.

Suggested Citation

  • James S. Fraser & Michael W. Clarkson & Sheena C. Degnan & Renske Erion & Dorothee Kern & Tom Alber, 2009. "Hidden alternative structures of proline isomerase essential for catalysis," Nature, Nature, vol. 462(7273), pages 669-673, December.
    • Handle: RePEc:nat:nature:v:462:y:2009:i:7273:d:10.1038_nature08615
    DOI: 10.1038/nature08615
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature08615
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature08615?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Antony D. St-Jacques & Joshua M. Rodriguez & Matthew G. Eason & Scott M. Foster & Safwat T. Khan & Adam M. Damry & Natalie K. Goto & Michael C. Thompson & Roberto A. Chica, 2023. "Computational remodeling of an enzyme conformational landscape for altered substrate selectivity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Tiberiu Teşileanu & Lucy J Colwell & Stanislas Leibler, 2015. "Protein Sectors: Statistical Coupling Analysis versus Conservation," PLOS Computational Biology, Public Library of Science, vol. 11(2), pages 1-20, February.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:462:y:2009:i:7273:d:10.1038_nature08615. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.