1g73

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[[Image:1g73.gif|left|200px]]
 
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{{Structure
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==CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN==
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|PDB= 1g73 |SIZE=350|CAPTION= <scene name='initialview01'>1g73</scene>, resolution 2.0&Aring;
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<StructureSection load='1g73' size='340' side='right'caption='[[1g73]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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<table><tr><td colspan='2'>[[1g73]] is a 4 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=1G73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1G73 FirstGlance]. <br>
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|ACTIVITY=
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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&#8491;</td></tr>
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|GENE= SMAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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|DOMAIN=
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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=1g73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g73 OCA], [https://pdbe.org/1g73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g73 RCSB], [https://www.ebi.ac.uk/pdbsum/1g73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g73 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1few|1FEW]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1g73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g73 OCA], [http://www.ebi.ac.uk/pdbsum/1g73 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1g73 RCSB]</span>
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== Disease ==
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}}
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[https://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[https://omim.org/entry/614152 614152]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref>
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== Function ==
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'''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''
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[https://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref> <ref>PMID:14523016</ref> <ref>PMID:15200957</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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Apoptosis is an essential process in the development and homeostasis of all metazoans. The inhibitor-of-apoptosis (IAP) proteins suppress cell death by inhibiting the activity of caspases; this inhibition is performed by the zinc-binding BIR domains of the IAP proteins. The mitochondrial protein Smac/DIABLO promotes apoptosis by eliminating the inhibitory effect of IAPs through physical interactions. Amino-terminal sequences in Smac/DIABLO are required for this function, as mutation of the very first amino acid leads to loss of interaction with IAPs and concomitant loss of Smac/DIABLO function. Here we report the high-resolution crystal structure of Smac/DIABLO complexed with the third BIR domain (BIR3) of XIAP. Our results show that the N-terminal four residues (Ala-Val-Pro-Ile) in Smac/DIABLO recognize a surface groove on BIR3, with the first residue Ala binding a hydrophobic pocket and making five hydrogen bonds to neighbouring residues on BIR3. These observations provide a structural explanation for the roles of the Smac N terminus as well as the conserved N-terminal sequences in the Drosophila proteins Hid/Grim/Reaper. In conjunction with other observations, our results reveal how Smac may relieve IAP inhibition of caspase-9 activity. In addition to explaining a number of biological observations, our structural analysis identifies potential targets for drug screening.
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g7/1g73_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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1G73 is a [[Protein complex]] structure of sequences 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=1G73 OCA].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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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=1g73 ConSurf].
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Structural basis of IAP recognition by Smac/DIABLO., Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X, Shi Y, Nature. 2000 Dec 21-28;408(6815):1008-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11140638 11140638]
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Chai, J.]]
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[[Category: Chai J]]
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[[Category: Shi, Y.]]
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[[Category: Shi Y]]
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[[Category: Suber, T L.]]
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[[Category: Suber TL]]
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[[Category: Wu, G.]]
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[[Category: Wu G]]
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[[Category: Wu, J W.]]
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[[Category: Wu J-W]]
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[[Category: helix bundle]]
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[[Category: zinc-binding domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:37:59 2008''
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Current revision

CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN

PDB ID 1g73

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