Substrate Specificities of Caspase Family Proteases*
- Robert V. Talanian‡,
- Christopher Quinlan,
- Simone Trautz,
- Maria C. Hackett,
- John A. Mankovich,
- David Banach,
- Tariq Ghayur,
- Kenneth D. Brady and
- Winnie W. Wong
- ‡ To whom correspondence should be addressed: BASF Bioresearch Corp., 100 Research Dr., Worcester, MA 01605. Tel.: 508-849-2581; Fax: 508-754-7784; E-mail: talanian{at}biovax.dnet.basf-ag.de
Abstract
The caspase family represents a new class of intracellular cysteine proteases with known or suspected roles in cytokine maturation and apoptosis. These enzymes display a preference for Asp in the P1 position of substrates. To clarify differences in the biological roles of the interleukin-1β converting enzyme (ICE) family proteases, we have examined in detail the specificities beyond the P1 position of caspase-1, −2, −3, −4, −6, and −7 toward minimal length peptide substrates in vitro We find differences and similarities between the enzymes that suggest a functional subgrouping of the family different from that based on overall sequence alignment. The primary specificities of ICE homologs explain many observed enzyme preferences for macromolecular substrates and can be used to support predictions of their natural function(s). The results also suggest the design of optimal peptidic substrates and inhibitors.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- ICE
-
interleukin-1β converting enzyme
- IL-1β
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interleukin-1β
- HPLC
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high performance liquid chromatography
- pNA
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p-nitroanilide
- Amc
-
aminomethylcoumarin
- Ac
-
acetyl
- Am
-
amide
- CHO
-
aldehyde.
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↵2 R. V. Talanian and C. Quinlan, unpublished results.
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↵3 T. Ghayur, unpublished results.
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- Received December 16, 1996.
- Revision received February 17, 1997.
- © 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
