Substrate specificities of caspase family proteases.
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-1beta 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.
Talanian
R V
RV
BASF Bioresearch Corp., Worcester, Massachusetts 01605, USA. talanian@biovax.dnet.basf-ag.de
Quinlan
C
C
Trautz
S
S
Hackett
M C
MC
Mankovich
J A
JA
Banach
D
D
Ghayur
T
T
Brady
K D
KD
Wong
W W
WW
D020170:Caspase 1; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D007700:Kinetics; D009842:Oligopeptides / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity
D005456:Fluorescent Dyes; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1