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| | <StructureSection load='3f7g' size='340' side='right'caption='[[3f7g]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3f7g' size='340' side='right'caption='[[3f7g]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f7g]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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> | + | <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> |
| - | </td></tr><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1oxn|1oxn]], [[1oxq|1oxq]], [[1oy7|1oy7]], [[3f7h|3f7h]], [[3f7i|3f7i]]</div></td></tr>
| + | <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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">also known as KIAP OR MLIAP OR LIVIN, BIRC7, KIAP, LIVIN, MLIAP, RNF50, UNQ5800/PRO19607/PRO21344 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=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> | | <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> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cohen, F]] | + | [[Category: Cohen F]] |
| - | [[Category: Fairbrother, W J]] | + | [[Category: Fairbrother WJ]] |
| - | [[Category: Franklin, M C]] | + | [[Category: Franklin MC]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Apoptosis inhibition]]
| + | |
| - | [[Category: Drug design]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Peptide complex]]
| + | |
| - | [[Category: Peptidomimetic]]
| + | |
| - | [[Category: Small molecule]]
| + | |
| - | [[Category: Zinc binding]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol. 2000 Nov 2;10(21):1359-66. PMID:11084335
- ↑ Ma L, Huang Y, Song Z, Feng S, Tian X, Du W, Qiu X, Heese K, Wu M. Livin promotes Smac/DIABLO degradation by ubiquitin-proteasome pathway. Cell Death Differ. 2006 Dec;13(12):2079-88. Epub 2006 May 26. PMID:16729033 doi:10.1038/sj.cdd.4401959
- ↑ Nachmias B, Lazar I, Elmalech M, Abed-El-Rahaman I, Asshab Y, Mandelboim O, Perlman R, Ben-Yehuda D. Subcellular localization determines the delicate balance between the anti- and pro-apoptotic activity of Livin. Apoptosis. 2007 Jul;12(7):1129-42. PMID:17294084 doi:10.1007/s10495-006-0049-1
- ↑ Nachmias B, Mizrahi S, Elmalech M, Lazar I, Ashhab Y, Gazit R, Markel G, Ben-Yehuda D, Mandelboim O. Manipulation of NK cytotoxicity by the IAP family member Livin. Eur J Immunol. 2007 Dec;37(12):3467-76. PMID:18034418 doi:10.1002/eji.200636600
- ↑ 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. Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold. J Med Chem. 2009 Mar 26;52(6):1723-30. PMID:19228017 doi:10.1021/jm801450c
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