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Crystal structure of an uncleaved serpin reveals the conformation of an inhibitory reactive loop

Nature Structural Biology volume 1, pages 251–258 (1994)Cite this article

Abstract

The three–dimensional structure of an uncleaved serpin, a variant of human antichymotrypsin engineered to be an inhibitor of human neutrophil elastase, has been determined by X–ray crystallographic methods and is currently being refined at 2.5 Å resolution. It contains an intact reactive loop in a distorted helical conformation. A comparison of the current model with that of its cleaved counterpart suggests that the conformational ‘stress’ of the serpin in its uncleaved and uncomplexed state may not be confined solely to the reactive loop or β–sheet A. It is intriguing that strand s4A is not pre–inserted into β–sheet A of the native serpin, and this has profound implications for the mechanism of serpin function.

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Authors and Affiliations

  1. Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Anzhi Wei, Barry S. Cooperman & David W. Christianson

  2. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Harvey Rubin

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Wei, A., Rubin, H., Cooperman, B. et al. Crystal structure of an uncleaved serpin reveals the conformation of an inhibitory reactive loop. Nat Struct Mol Biol 1, 251–258 (1994). https://doi.org/10.1038/nsb0494-251

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