IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v423y2003i6941d10.1038_nature01681.html
   My bibliography  Save this article

Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B

Author

Listed:
  • Rob L. M. van Montfort

    (Astex Technology Ltd)

  • Miles Congreve

    (Astex Technology Ltd)

  • Dominic Tisi

    (Astex Technology Ltd)

  • Robin Carr

    (Astex Technology Ltd)

  • Harren Jhoti

    (Astex Technology Ltd)

Abstract

Protein tyrosine phosphatases regulate signal transduction pathways involving tyrosine phosphorylation1 and have been implicated in the development of cancer, diabetes, rheumatoid arthritis and hypertension2. Increasing evidence suggests that the cellular redox state is involved in regulating tyrosine phosphatase activity through the reversible oxidization of the catalytic cysteine to sulphenic acid (Cys-SOH)3,4,5,6. But how further oxidation to the irreversible sulphinic (Cys-SO2H) and sulphonic (Cys-SO3H) forms is prevented remains unclear. Here we report the crystal structures of the regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), an important enzyme in the negative regulation of the insulin receptor7,8 and a therapeutic target in type II diabetes and obesity9. We also identify a sulphenyl-amide species that is formed through oxidation of its catalytic cysteine. Formation of the sulphenyl-amide causes large changes in the PTP1B active site, which are reversible by reduction with the cellular reducing agent glutathione. The sulphenyl-amide is a protective intermediate in the oxidative inhibition of PTP1B. In addition, it may facilitate reactivation of PTP1B by biological thiols and signal a unique state of the protein.

Suggested Citation

  • Rob L. M. van Montfort & Miles Congreve & Dominic Tisi & Robin Carr & Harren Jhoti, 2003. "Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B," Nature, Nature, vol. 423(6941), pages 773-777, June.
    • Handle: RePEc:nat:nature:v:423:y:2003:i:6941:d:10.1038_nature01681
    DOI: 10.1038/nature01681
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature01681
    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/nature01681?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. Gaurav Dwivedi & Margaret A Gran & Pritha Bagchi & Melissa L Kemp, 2015. "Dynamic Redox Regulation of IL-4 Signaling," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-20, November.
    2. Dilek Eren & Burak Alakent, 2013. "Frequency Response of a Protein to Local Conformational Perturbations," PLOS Computational Biology, Public Library of Science, vol. 9(9), pages 1-15, September.

    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:423:y:2003:i:6941:d:10.1038_nature01681. 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.