1ibc: Difference between revisions

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.

1IBC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ACE as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] Structure known Active Sites: S1, S2, S3 and S4. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IBC OCA].  

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