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Analogous inhibitors of elastase do not always bind analogously

Nature Structural Biology volume 1, pages 55–58 (1994)Cite this article

Abstract

It has been assumed that the structure of a single inhibitor complex is sufficient to define the available subsites of an enzyme that has a unique binding site and a uniquely defined mode for ligand binding — the specificity for these subsites can thus be probed by kinetic experiments. Elastase is an enzyme for which these traditional assumptions, which underlie such structural and kinetic studies, do not hold. Three new crystal structures of elastase complexed to chemically similar inhibitors with similar binding affinities reveal a diversity of binding modes as well as two new subsites on elastase. The existence of multiple binding sites and different binding modes for such similar inhibitors indicates that researchers must proceed with caution when using kinetics to map out protein subsites.

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Authors and Affiliations

  1. Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, 02254, USA

    Carla Mattos, Bjarne Rasmussen, Xiaochun Ding, Gregory A. Petsko & Dagmar Ringe

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  1. Carla Mattos
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  2. Bjarne Rasmussen
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  3. Xiaochun Ding
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  4. Gregory A. Petsko
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Mattos, C., Rasmussen, B., Ding, X. et al. Analogous inhibitors of elastase do not always bind analogously. Nat Struct Mol Biol 1, 55–58 (1994). https://doi.org/10.1038/nsb0194-55

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