3f7g

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[[Image:3f7g.png|left|200px]]
 
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==Structure of the BIR domain from ML-IAP bound to a peptidomimetic==
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The line below this paragraph, containing "STRUCTURE_3f7g", creates the "Structure Box" on the page.
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<StructureSection load='3f7g' size='340' side='right'caption='[[3f7g]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3f7g]] is a 5 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=3F7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F7G FirstGlance]. <br>
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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]] 2.3&#8491;</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=389:L-ALANYL-L-VALYL-N-(2,2-DIPHENYLETHYL)-L-PROLINAMIDE'>389</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3f7g| PDB=3f7g | SCENE= }}
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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=3f7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f7g OCA], [https://pdbe.org/3f7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f7g RCSB], [https://www.ebi.ac.uk/pdbsum/3f7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f7g ProSAT]</span></td></tr>
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</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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f7/3f7g_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</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/main_output.php?pdb_ID=3f7g ConSurf].
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<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 an azabicyclooctane scaffold was designed and synthesized. The most potent of these compounds, 14b, binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domain of c-IAP1 with K(i) values of 140, 38, and 33 nM, respectively. These compounds promote degradation of c-IAP1, activate caspases, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Finally, compound 14b inhibits tumor growth when dosed orally in a breast cancer xenograft model.
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===Structure of the BIR domain from ML-IAP bound to a peptidomimetic===
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Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.,Cohen F, Alicke B, Elliott LO, Flygare JA, Goncharov T, Keteltas SF, Franklin MC, Frankovitz S, Stephan JP, Tsui V, Vucic D, Wong H, Fairbrother WJ J Med Chem. 2009 Mar 26;52(6):1723-30. PMID:19228017<ref>PMID:19228017</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>
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The line below this paragraph, {{ABSTRACT_PUBMED_19228017}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 3f7g" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 19228017 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19228017}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3f7g]] is a 5 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=3F7G OCA].
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==Reference==
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<ref group="xtra">PMID:19228017</ref><ref group="xtra">PMID:17168540</ref><ref group="xtra">PMID:15485396</ref><references group="xtra"/>
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[[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: Alternative splicing]]
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[[Category: Franklin MC]]
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[[Category: Apoptosis]]
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[[Category: Apoptosis inhibition]]
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[[Category: Cytoplasm]]
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[[Category: Drug design]]
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[[Category: Metal-binding]]
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[[Category: Nucleus]]
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[[Category: Peptide complex]]
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[[Category: Peptidomimetic]]
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[[Category: Polymorphism]]
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[[Category: Small molecule]]
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[[Category: Zinc]]
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[[Category: Zinc binding]]
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[[Category: Zinc-finger]]
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Current revision

Structure of the BIR domain from ML-IAP bound to a peptidomimetic

PDB ID 3f7g

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