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Inhibitory conformation of the reactive loop of α1-antitrypsin

Nature Structural Biology volume 3, pages 676–681 (1996)Cite this article

Abstract

The reactive site loop of the serpin family of serine proteinase inhibitors is flexible and can adopt a number of diverse conformations. A 2.9 Å resolution structure of α1-antitrypsin—the principal proteinase inhibitor in human plasma—shows the loop in a stable canonical conformation matching that found in all other families of serine proteinase inhibitors. This unexpected finding in the absence of loop insertion into the body of the molecule favours a two-stage mechanism of inhibition and provides a model for the heparin activation of antithrombin. The β-pleated strand conformation of the loop also accounts for the polymerization of the serpins in disease and for their association with other β-sheet structures, most notably the β-amyloid of Alzheimer's disease.

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Authors and Affiliations

  1. Departments of Haematology, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Peter R. Elliott, David A. Lomas & Robin W. Carrell

  2. Departments of Medicine, University of Cambridge, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Peter R. Elliott & David A. Lomas

  3. Departments of Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

    Jan Pieter Abrahams

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  2. David A. Lomas
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  3. Robin W. Carrell
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  4. Jan Pieter Abrahams
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Elliott, P., Lomas, D., Carrell, R. et al. Inhibitory conformation of the reactive loop of α1-antitrypsin. Nat Struct Mol Biol 3, 676–681 (1996). https://doi.org/10.1038/nsb0896-676

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