IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms4110.html
   My bibliography  Save this article

Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer

Author

Listed:
  • Shixuan Liu

    (Washington University School of Medicine)

  • Wei Cheng

    (Washington University School of Medicine)

  • Ronald Fowle Grider

    (Washington University School of Medicine)

  • Guomin Shen

    (Washington University School of Medicine)

  • Weikai Li

    (Washington University School of Medicine)

Abstract

The intramembrane vitamin K epoxide reductase (VKOR) supports blood coagulation in humans and is the target of the anticoagulant warfarin. VKOR and its homologues generate disulphide bonds in organisms ranging from bacteria to humans. Here, to better understand the mechanism of VKOR catalysis, we report two crystal structures of a bacterial VKOR captured in different reaction states. These structures reveal a short helix at the hydrophobic active site of VKOR that alters between wound and unwound conformations. Motions of this ‘horizontal helix’ promote electron transfer by regulating the positions of two cysteines in an adjacent loop. Winding of the helix separates these ‘loop cysteines’ to prevent backward electron flow. Despite these motions, hydrophobicity at the active site is maintained to facilitate VKOR catalysis. Biochemical experiments suggest that several warfarin-resistant mutations act by changing the conformation of the horizontal helix. Taken together, these studies provide a comprehensive understanding of VKOR function.

Suggested Citation

  • Shixuan Liu & Wei Cheng & Ronald Fowle Grider & Guomin Shen & Weikai Li, 2014. "Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer," Nature Communications, Nature, vol. 5(1), pages 1-9, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4110
    DOI: 10.1038/ncomms4110
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms4110
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms4110?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
    ---><---

    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:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4110. 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.