View source for 2esp


==Human ubiquitin-conjugating enzyme (E2) UbcH5b mutant Ile88Ala==
<StructureSection load='2esp' size='340' side='right'caption='[[2esp]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2esp]] is a 1 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=2ESP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ESP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.52&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></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=2esp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2esp OCA], [https://pdbe.org/2esp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2esp RCSB], [https://www.ebi.ac.uk/pdbsum/2esp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2esp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</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/es/2esp_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=2esp ConSurf].
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== Publication Abstract from PubMed ==
Ubiquitin-conjugating enzymes (E2s) collaborate with the ubiquitin-activating enzyme (E1) and ubiquitin ligases (E3s) to attach ubiquitin to target proteins. RING-containing E3s simultaneously bind to E2s and substrates, bringing them into close proximity and thus facilitating ubiquitination. We show herein that, although the E3-binding site on the human E2 UbcH5b is distant from its active site, two RING-type minimal E3 modules lacking substrate-binding functions greatly stimulate the rate of ubiquitin release from the UbcH5b-ubiquitin thioester. Using statistical coupling analysis and mutagenesis, we identify and characterize clusters of coevolving and functionally linked residues within UbcH5b that span its E3-binding and active sites. Several UbcH5b mutants are defective in their stimulation by E3s despite their abilities to bind to these E3s, to form ubiquitin thioesters, and to release ubiquitin at a basal rate. One such mutation, I37A, is distant from both the active site and the E3-binding site of UbcH5b. Our studies reveal structural determinants for communication between distal functional sites of E2s and suggest that RING-type E3s activate E2s allosterically.

Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases.,Ozkan E, Yu H, Deisenhofer J Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18890-5. Epub 2005 Dec 19. PMID:16365295<ref>PMID:16365295</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Deisenhofer J]]
[[Category: Ozkan E]]
[[Category: Yu H]]