1ibc: Difference between revisions
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[[Image:1ibc.gif|left|200px]]<br /> | [[Image:1ibc.gif|left|200px]]<br /><applet load="1ibc" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1ibc" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1ibc, resolution 2.73Å" /> | caption="1ibc, resolution 2.73Å" /> | ||
'''CRYSTAL STRUCTURE OF INHIBITED INTERLEUKIN-1BETA CONVERTING ENZYME'''<br /> | '''CRYSTAL STRUCTURE OF INHIBITED INTERLEUKIN-1BETA CONVERTING ENZYME'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
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] | 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] Known structural/functional Sites: <scene name='pdbsite=S1:Inhibitor Binding Sub-Site S1'>S1</scene>, <scene name='pdbsite=S2:Inhibitor Binding Sub-Site S2'>S2</scene>, <scene name='pdbsite=S3:Inhibitor Binding Sub-Site S3'>S3</scene> and <scene name='pdbsite=S4:Inhibitor Binding Sub-Site S4'>S4</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IBC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protease]] | [[Category: protease]] | ||
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Revision as of 17:23, 18 December 2007
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CRYSTAL STRUCTURE OF INHIBITED INTERLEUKIN-1BETA CONVERTING ENZYME
OverviewOverview
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.
About this StructureAbout this Structure
1IBC is a Single protein structure of sequence from Homo sapiens with ACE as ligand. Active as Caspase-1, with EC number 3.4.22.36 Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
ReferenceReference
A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE)., Rano TA, Timkey T, Peterson EP, Rotonda J, Nicholson DW, Becker JW, Chapman KT, Thornberry NA, Chem Biol. 1997 Feb;4(2):149-55. PMID:9190289
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