We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

1g73

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1g73" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g73, resolution 2.0&Aring;" /> '''CRYSTAL STRUCTURE OF...)
Current revision (07:23, 7 February 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1g73.gif|left|200px]]<br />
 
-
<applet load="1g73" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1g73, resolution 2.0&Aring;" />
 
-
'''CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN'''<br />
 
-
==Overview==
+
==CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN==
-
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.
+
<StructureSection load='1g73' size='340' side='right'caption='[[1g73]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-
 
+
== Structural highlights ==
-
==Disease==
+
<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>
-
Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300079 300079]]
+
</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>
-
 
+
<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>
-
==About this Structure==
+
<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>
-
1G73 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1G73 OCA].
+
</table>
-
 
+
== Disease ==
-
==Reference==
+
[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>
-
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=11140638 11140638]
+
== Function ==
 +
[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>
 +
== 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/g7/1g73_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/main_output.php?pdb_ID=1g73 ConSurf].
 +
<div style="clear:both"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Protein complex]]
+
[[Category: Large Structures]]
-
[[Category: Chai, J.]]
+
[[Category: Chai J]]
-
[[Category: Shi, Y.]]
+
[[Category: Shi Y]]
-
[[Category: Suber, T.L.]]
+
[[Category: Suber TL]]
-
[[Category: Wu, G.]]
+
[[Category: Wu G]]
-
[[Category: Wu, J.W.]]
+
[[Category: Wu J-W]]
-
[[Category: ZN]]
+
-
[[Category: helix bundle]]
+
-
[[Category: zinc-binding domain]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:01:19 2007''
+

Current revision

CRYSTAL STRUCTURE OF SMAC BOUND TO XIAP-BIR3 DOMAIN

PDB ID 1g73

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools