Substrate Specificities of Caspase Family Proteases

• Published in: The Journal of biological chemistry 1997-04, Vol.272 (15), p.9677-9682
• Main Authors: Talanian, R V, Quinlan, C, Trautz, S, Hackett, M C, Mankovich, J A, Banach, D, Ghayur, T, Brady, K D, Wong, W W
• Format: Article
• Language: English
• Subjects: Caspase 1; Caspase 3; Caspase 6; Caspase 7; Caspases; Chromatography, High Pressure Liquid; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - metabolism; Fluorescent Dyes - metabolism; Kinetics; Oligopeptides - metabolism; Signal Transduction; Substrate Specificity
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.15.9677

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.