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The intact and cleaved human antithrombin III complex as a model for serpin–proteinase interactions

Nature Structural & Molecular Biologyvolume 1pages4854 (1994) | Download Citation



Antithrombin is a member of the serine proteinase inhibitor (serpin) family which contain a flexible reactive site loop that interacts with, and is cleaved by the target proteinase. In cleaved and latent serpins, the reactive site loop is inserted into a large central β–sheet in the same molecule, whereas in ovalbumin, a nonfunctional serpin, the reactive site loop is completely exposed and in an α–helical conformation. However, in neither conformation can the reactive site loop bind to target proteinases. Here we report the structure of an intact and cleaved human antithrombin complex. The intact reactive site loop is in a novel conformation that seems well suited for interaction with proteinases such as thrombin and blood coagulation factor Xa.

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Author notes

    • Herman A. Schreuder

    Present address: Marion Merrell Dow Research Institute, Strasbourg Research center, 16, Rued'Ankara, 67000, Strasbourg, France

    • Wim G. J. Hol

    Present address: School of Medicine, Department of Biological Structure, Health Sciences Building, SM-20, University of Washington, Seattle, WA, 98195, USA


  1. BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747AG, Groningen, The Netherlands

    • Herman A. Schreuder
    • , Bijtske de Boer
    •  & Wim G. J. Hol
  2. Organon International BV, P.O. Box 20, 5340 BH, Oss, The Netherlands

    • Rein Dijkema
    • , John Mulders
    • , Henri J. M. Theunissen
    •  & Peter D. J. Grootenhuis


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