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The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis

Nature Structural Biology volume 3, pages 619–625 (1996)Cite this article

Abstract

Cysteine proteases related to mammalian interleukin-1β converting enzyme (ICE) and to its Caenorhabditis elegans homologue, CED-3, play a critical role in the biochemical events that culminate in apoptosis. We have determined the three-dimensional structure of a complex of the human CED-3 homologue CPP32/apopain with a potent tetrapeptide-aldehyde inhibitor. The protein resembles ICE in overall structure, but its S4 subsite is strikingly different in size and chemical composition. These differences account for the variation in specificity between the ICE- and CED-3-related proteases and enable the design of specific inhibitors that can probe the physiological functions of the proteins and disease states with which they are associated.

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Authors and Affiliations

  1. Department of Biochemistry, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey, 07065-0900, USA

    Jennifer Rotonda, Erin P. Peterson, Nancy A. Thornberry & Joseph W. Becker

  2. Departments of Biochemistry and Molecular Biology, Merck-Frosst Centre for Therapeutic Research, Box 1005, PointeClaire-Dorval, Québec, H9R4P8, Canada

    Donald W. Nicholson, Kimberly M. Fazil, Dita M. Rasper & John P. Vaillancourt

  3. Medicinal Chemistry, Merck-Frosst Centre for Therapeutic Research, Box 1005, PointeClaire-Dorval, Québec, H9R4P8, Canada

    Michel Gallant, Yves Gareau, Marc Labelle & Réjean Ruel

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Rotonda, J., Nicholson, D., Fazil, K. et al. The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis. Nat Struct Mol Biol 3, 619–625 (1996). https://doi.org/10.1038/nsb0796-619

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