1rwm: Difference between revisions

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-[[Image:1rwm.png|left|200px]]
+==Crystal structure of human caspase-1 in complex with 4-oxo-3-[2-(5-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-thiophen-2-yl)-acetylamino]-pentanoic acid==
+<StructureSection load='1rwm' size='340' side='right' caption='[[1rwm]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1rwm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RWM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RWM FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q2Y:4-OXO-3-[2-(5-{[4-(QUINOXALIN-2-YLAMINO)-BENZOYLAMINO]-METHYL}-THIOPHEN-2-YL)-ACETYLAMINO]-PENTANOIC+ACID'>Q2Y</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ice|1ice]], [[1bmq|1bmq]], [[1ibc|1ibc]], [[1rwk|1rwk]], [[1rwn|1rwn]], [[1rwo|1rwo]], [[1rwp|1rwp]], [[1rwv|1rwv]], [[1rww|1rww]], [[1rwx|1rwx]]</td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP1, IL1BC, IL1BCE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rwm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rwm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rwm RCSB], [http://www.ebi.ac.uk/pdbsum/1rwm PDBsum]</span></td></tr>
+<table>
+== 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/1rwm_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Caspase-1 is a key endopeptidase responsible for the post-translational processing of the IL-1beta and IL-18 cytokines and small-molecule inhibitors that modulate the activity of this enzyme are predicted to be important therapeutic treatments for many inflammatory diseases. A fragment-assembly approach, accompanied by structural analysis, was employed to generate caspase-1 inhibitors. With the aid of Tethering with extenders (small molecules that bind to the active-site cysteine and contain a free thiol), two novel fragments that bound to the active site and made a disulfide bond with the extender were identified by mass spectrometry. Direct linking of each fragment to the extender generated submicromolar reversible inhibitors that significantly reduced secretion of IL-1beta but not IL-6 from human peripheral blood mononuclear cells. Thus, Tethering with extenders facilitated rapid identification and synthesis of caspase-1 inhibitors with cell-based activity and subsequent structural analyses provided insights into the enzyme's ability to accommodate different inhibitor-binding modes in the active site.
-{{STRUCTURE_1rwm|  PDB=1rwm  |  SCENE=  }}
+Structural analysis of caspase-1 inhibitors derived from Tethering.,O'Brien T, Fahr BT, Sopko MM, Lam JW, Waal ND, Raimundo BC, Purkey HE, Pham P, Romanowski MJ Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 May 1;61(Pt, 5):451-8. Epub 2005 Apr 9. PMID:16511067<ref>PMID:16511067</ref>
-===Crystal structure of human caspase-1 in complex with 4-oxo-3-[2-(5-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-thiophen-2-yl)-acetylamino]-pentanoic acid===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_16511067}}
-==About this Structure==
-[[1rwm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RWM OCA].
 ==See Also==
 *[[Caspase|Caspase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:016511067</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Caspase-1]]
 [[Category: Homo sapiens]]