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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
E.C.3.4.22.36
- caspase-1.
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Reaction:
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Release of interleukin 1-beta by specific cleavage at 116-Asp-|-Ala-117 and 27-Asp-|-Gly-28 bonds in precursor. Also hydrolyzes the small- molecule substrate, Ac-Tyr-Val-Ala-Asp-|-NHMec.
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Chem Biol
4:149-155
(1997)
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PubMed id:
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A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE).
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T.A.Rano,
T.Timkey,
E.P.Peterson,
J.Rotonda,
D.W.Nicholson,
J.W.Becker,
K.T.Chapman,
N.A.Thornberry.
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ABSTRACT
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BACKGROUND: Interleukin-1beta converting enzyme (ICE/caspase-1) is the protease
responsible for interleukin-1beta (IL-1beta) production in monocytes. It was the
first member of a new cysteine protease family to be identified. Members of this
family have functions in both inflammation and apoptosis. RESULTS: A novel
method for identifying protease specificity, employing a positional-scanning
substrate library, was used to determine the amino-acid preferences of ICE.
Using this method, the complete specificity of a protease can be mapped in the
time required to perform one assay. The results indicate that the optimal
tetrapeptide recognition sequence for ICE is WEHD, not YVAD, as previously
believed, and this led to the synthesis of an unusually potent aldehyde
inhibitor, Ac-WEHD-CHO (Ki = 56 pM). The structural basis for this potent
inhibition was determined by X-ray crystallography. CONCLUSIONS: The results
presented in this study establish a positional-scanning library as a powerful
tool for rapidly and accurately assessing protease specificity. The preferred
sequence for ICE (WEHD) differs significantly from that found in human
pro-interleukin-1beta (YVHD), which suggests that this protease may have
additional endogenous substrates, consistent with evidence linking it to
apoptosis and IL-1alpha production.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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PDB codes:
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PDB codes:
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PDB code:
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PDB codes:
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|
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A.F.Kisselev,
M.Garcia-Calvo,
H.S.Overkleeft,
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PDB code:
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|
D.A.Erlanson,
J.W.Lam,
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(1998).
Inhibition of human caspases by peptide-based and macromolecular inhibitors.
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STAT1 is inactivated by a caspase.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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