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[[Image:1rww.gif|left|200px]]<br /><applet load="1rww" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1rww, resolution 2.80&Aring;" />
'''Crystal structure of human caspase-1 in complex with 4-oxo-3-[(6-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-pyridine-3-carbonyl)-amino]-butyric acid'''<br />


==Overview==
==Crystal structure of human caspase-1 in complex with 4-oxo-3-[(6-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-pyridine-3-carbonyl)-amino]-butyric acid==
Disulfide Tethering was applied to the active site of human caspase-1, resulting in the discovery of a novel, tricyclic molecular fragment that, selectively binds in S4. This fragment was developed into a class of, potent inhibitors of human caspase-1. Several key analogues determined the, optimal distance of the tricycle from the catalytic residues, the relative, importance of various features of the tricycle, and the importance of the, linker.
<StructureSection load='1rww' size='340' side='right'caption='[[1rww]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1rww]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RWW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OQB:4-OXO-3-[(6-{[4-(QUINOXALIN-2-YLAMINO)-BENZOYLAMINO]-METHYL}-PYRIDINE-3-CARBONYL)-AMINO]-BUTYRIC+ACID'>OQB</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rww OCA], [https://pdbe.org/1rww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rww RCSB], [https://www.ebi.ac.uk/pdbsum/1rww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rww ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CASP1_HUMAN CASP1_HUMAN] Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.<ref>PMID:7876192</ref> <ref>PMID:15498465</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rw/1rww_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rww ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Disulfide Tethering was applied to the active site of human caspase-1, resulting in the discovery of a novel, tricyclic molecular fragment that selectively binds in S4. This fragment was developed into a class of potent inhibitors of human caspase-1. Several key analogues determined the optimal distance of the tricycle from the catalytic residues, the relative importance of various features of the tricycle, and the importance of the linker.


==About this Structure==
Tethering identifies fragment that yields potent inhibitors of human caspase-1.,Fahr BT, O'Brien T, Pham P, Waal ND, Baskaran S, Raimundo BC, Lam JW, Sopko MM, Purkey HE, Romanowski MJ Bioorg Med Chem Lett. 2006 Feb;16(3):559-62. Epub 2005 Nov 4. PMID:16274992<ref>PMID:16274992</ref>
1RWW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=OQB:'>OQB</scene> 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RWW OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Tethering identifies fragment that yields potent inhibitors of human caspase-1., Fahr BT, O'Brien T, Pham P, Waal ND, Baskaran S, Raimundo BC, Lam JW, Sopko MM, Purkey HE, Romanowski MJ, Bioorg Med Chem Lett. 2006 Feb;16(3):559-62. Epub 2005 Nov 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16274992 16274992]
</div>
[[Category: Caspase-1]]
<div class="pdbe-citations 1rww" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Brien, T.O.]]
[[Category: Fahr BT]]
[[Category: Fahr, B.T.]]
[[Category: O'Brien T]]
[[Category: Romanowski, M.J.]]
[[Category: Romanowski MJ]]
[[Category: OQB]]
[[Category: hydrolase]]
[[Category: protein-small molecule inhibitor complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:30:35 2008''

Latest revision as of 07:21, 30 October 2024

Crystal structure of human caspase-1 in complex with 4-oxo-3-[(6-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-pyridine-3-carbonyl)-amino]-butyric acid

1rww, resolution 2.80Å

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