3rz3

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{{STRUCTURE_3rz3| PDB=3rz3 | SCENE= }}
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==Human Cdc34 E2 in complex with CC0651 inhibitor==
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===Human Cdc34 E2 in complex with CC0651 inhibitor===
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<StructureSection load='3rz3' size='340' side='right' caption='[[3rz3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21683433}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3rz3]] is a 4 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=3RZ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RZ3 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=U94:4,5-DIDEOXY-5-(3,5-DICHLOROBIPHENYL-4-YL)-4-[(METHOXYACETYL)AMINO]-L-ARABINONIC+ACID'>U94</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ob4|2ob4]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC34, UBCH3, UBE2R1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rz3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rz3 RCSB], [http://www.ebi.ac.uk/pdbsum/3rz3 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In the ubiquitin-proteasome system (UPS), E2 enzymes mediate the conjugation of ubiquitin to substrates and thereby control protein stability and interactions. The E2 enzyme hCdc34 catalyzes the ubiquitination of hundreds of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes. We identified a small molecule termed CC0651 that selectively inhibits hCdc34. Structure determination revealed that CC0651 inserts into a cryptic binding pocket on hCdc34 distant from the catalytic site, causing subtle but wholesale displacement of E2 secondary structural elements. CC0651 analogs inhibited proliferation of human cancer cell lines and caused accumulation of the SCF(Skp2) substrate p27(Kip1). CC0651 does not affect hCdc34 interactions with E1 or E3 enzymes or the formation of the ubiquitin thioester but instead interferes with the discharge of ubiquitin to acceptor lysine residues. E2 enzymes are thus susceptible to noncatalytic site inhibition and may represent a viable class of drug target in the UPS.
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==Function==
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An allosteric inhibitor of the human cdc34 ubiquitin-conjugating enzyme.,Ceccarelli DF, Tang X, Pelletier B, Orlicky S, Xie W, Plantevin V, Neculai D, Chou YC, Ogunjimi A, Al-Hakim A, Varelas X, Koszela J, Wasney GA, Vedadi M, Dhe-Paganon S, Cox S, Xu S, Lopez-Girona A, Mercurio F, Wrana J, Durocher D, Meloche S, Webb DR, Tyers M, Sicheri F Cell. 2011 Jun 24;145(7):1075-87. Epub 2011 Jun 16. PMID:21683433<ref>PMID:21683433</ref>
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[[http://www.uniprot.org/uniprot/UB2R1_HUMAN UB2R1_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes.<ref>PMID:10329681</ref> <ref>PMID:10373550</ref> <ref>PMID:10871850</ref> <ref>PMID:11675391</ref> <ref>PMID:12037680</ref> <ref>PMID:15652359</ref> <ref>PMID:17461777</ref> <ref>PMID:17698585</ref> <ref>PMID:19945379</ref> <ref>PMID:19126550</ref> <ref>PMID:20061386</ref> <ref>PMID:20347421</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3rz3]] is a 4 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=3RZ3 OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:021683433</ref><references group="xtra"/><references/>
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*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
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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]]
[[Category: Ubiquitin--protein ligase]]
[[Category: Ubiquitin--protein ligase]]
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[[Category: Ceccarelli, D F.]]
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[[Category: Ceccarelli, D F]]
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[[Category: Sicheri, F.]]
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[[Category: Sicheri, F]]
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[[Category: Webb, D R.]]
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[[Category: Webb, D R]]
[[Category: E2 domain]]
[[Category: E2 domain]]
[[Category: Ligase-ligase inhibitor complex]]
[[Category: Ligase-ligase inhibitor complex]]
[[Category: Ubiquitin conjugating enzyme domain]]
[[Category: Ubiquitin conjugating enzyme domain]]

Revision as of 10:57, 19 December 2014

Human Cdc34 E2 in complex with CC0651 inhibitor

3rz3, resolution 2.30Å

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