3gt9

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==Structure of an ML-IAP/XIAP chimera bound to a peptidomimetic==
==Structure of an ML-IAP/XIAP chimera bound to a peptidomimetic==
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<StructureSection load='3gt9' size='340' side='right' caption='[[3gt9]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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<StructureSection load='3gt9' size='340' side='right'caption='[[3gt9]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3gt9]] 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=3GT9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GT9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3gt9]] 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=3GT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GT9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=516:N-{(1S)-1-CYCLOHEXYL-2-[(2S)-2-(4-NAPHTHALEN-1-YL-1,3-THIAZOL-2-YL)PYRROLIDIN-1-YL]-2-OXOETHYL}-N~2~-METHYL-L-ALANINAMIDE'>516</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f7h|3f7h]], [[3f7i|3f7i]], [[3f7g|3f7g]], [[2i3h|2i3h]], [[2i3i|2i3i]], [[1tw6|1tw6]], [[3gta|3gta]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=516:N-{(1S)-1-CYCLOHEXYL-2-[(2S)-2-(4-NAPHTHALEN-1-YL-1,3-THIAZOL-2-YL)PYRROLIDIN-1-YL]-2-OXOETHYL}-N~2~-METHYL-L-ALANINAMIDE'>516</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BIRC7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gt9 OCA], [https://pdbe.org/3gt9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gt9 RCSB], [https://www.ebi.ac.uk/pdbsum/3gt9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gt9 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gt9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gt9 RCSB], [http://www.ebi.ac.uk/pdbsum/3gt9 PDBsum]</span></td></tr>
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</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BIRC7_HUMAN BIRC7_HUMAN] Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions. Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and NR2C2/TAK1. In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9. Isoform 1 blocks staurosporine-induced apoptosis. Isoform 2 blocks etoposide-induced apoptosis. Isoform 2 protects against natural killer (NK) cell killing whereas isoform 1 augments killing.<ref>PMID:11084335</ref> <ref>PMID:16729033</ref> <ref>PMID:17294084</ref> <ref>PMID:18034418</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gt/3gt9_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gt/3gt9_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</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].
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</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=3gt9 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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A series of IAP antagonists based on thiazole or benzothiazole amide isosteres was designed and synthesized. These compounds were tested for binding to the XIAP-BIR3 and ML-IAP BIR using a fluorescence polarization assay. The most potent of these compounds, 19a and 33b, were found to have K(i)'s of 20-30 nM against ML-IAP and 50-60 nM against XIAP-BIR3.
 
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Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres.,Cohen F, Koehler MF, Bergeron P, Elliott LO, Flygare JA, Franklin MC, Gazzard L, Keteltas SF, Lau K, Ly CQ, Tsui V, Fairbrother WJ Bioorg Med Chem Lett. 2010 Apr 1;20(7):2229-33. Epub 2010 Feb 8. PMID:20189383<ref>PMID:20189383</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cohen, F]]
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[[Category: Large Structures]]
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[[Category: Fairbrother, W J]]
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[[Category: Cohen F]]
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[[Category: Franklin, M C]]
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[[Category: Fairbrother WJ]]
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[[Category: Apoptosis]]
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[[Category: Franklin MC]]
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[[Category: Apoptosis inhibition]]
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[[Category: Drug design]]
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[[Category: Metal-binding]]
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[[Category: Peptide complex]]
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[[Category: Peptidomimetic]]
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[[Category: Small molecule]]
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[[Category: Zinc binding]]
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Current revision

Structure of an ML-IAP/XIAP chimera bound to a peptidomimetic

PDB ID 3gt9

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Proteopedia Page Contributors and Editors (what is this?)

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