Mobile reactive centre of serpins and the control of thrombosis (original) (raw)

Nature volume 353, pages 576–578 (1991)Cite this article

A Correction to this article was published on 19 August 1993

Abstract

Two protease inhibitors in human plasma play a key part in the control of thrombosis: antithrombin inhibits coagulation and the plasminogen activator inhibitor PAI-1 inhibits fibrinolysis, the dissolving of clots. Both inhibitors are members of the serpin family and both exist in the plasma in latent or inactive forms. We show here that the reactive centre of the serpins can adopt varying conformations and that mobility of the reactive centre is necessary for the function of antithrombin and its binding and activation by heparin; the identification of a new locked conformation explains the latent inactive state of PAI-1. This ability to vary conformation not only allows the modulation of inhibitory activity but also protects the circulating inhibitor against proteolytic attack. Together these findings explain the retention by the serpins of a large and unconstrained reactive centre as compared to the small fixed peptide loop of other families of serine protease inhibitors.

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Authors and Affiliations

  1. Department of Haematology, University of Cambridge, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK
    Robin W. Carrell, Dyfed Ll. Evans & Penelope E. Stein

Authors

  1. Robin W. Carrell
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  2. Dyfed Ll. Evans
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  3. Penelope E. Stein
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Carrell, R., Evans, D. & Stein, P. Mobile reactive centre of serpins and the control of thrombosis.Nature 353, 576–578 (1991). https://doi.org/10.1038/353576a0

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