3rz3 - Revision history

OCA at 12:40, 14 March 2024

2024-03-14T12:40:49Z

←Older revision		Revision as of 12:40, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3rz3' size='340' side='right'caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3rz3' size='340' side='right'caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3rz3]] is a 4 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=3RZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZ3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3rz3]] 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=3RZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZ3 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=U94:4,5~~-~~DIDEOXY-5-(3~~,~~5-DICHLOROBIPHENYL-4-YL)-4-~~[~~(METHOXYACETYL)AMINO]-L-ARABINONIC+ACID'>U94</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;'>[[2ob4\|2ob4]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U94:4,5-DIDEOXY-5-(3,5-DICHLOROBIPHENYL-4-YL)-4-[(METHOXYACETYL)AMINO]-L-ARABINONIC+ACID'>U94</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CDC34, UBCH3, UBE2R1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Ubiquitin~~--~~protein_ligase Ubiquitin~~--~~protein ligase~~]~~, with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19]~~ </~~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=3rz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rz3 OCA], [https://pdbe.org/3rz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rz3 RCSB], [https://www.ebi.ac.uk/pdbsum/3rz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rz3 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=3rz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rz3 OCA], [https://pdbe.org/3rz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rz3 RCSB], [https://www.ebi.ac.uk/pdbsum/3rz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rz3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://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>	+	[https://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>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	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.	+
-		+
-	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>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3rz3" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 28:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Ubiquitin--protein ligase]]~~	+	[[Category: Ceccarelli DF]]
-	[[Category: Ceccarelli~~, D F~~]]	+	[[Category: Sicheri F]]
-	[[Category: Sicheri, F]]	+	[[Category: Webb DR]]
-	[[Category: Webb~~, D R]]~~	+
-	~~[[Category: E2 domain]]~~	+
-	~~[[Category: Ligase-ligase inhibitor complex]]~~	+
-	~~[[Category: Ubiquitin conjugating enzyme domain~~]]	+

OCA at 10:31, 22 June 2022

2022-06-22T10:31:03Z

←Older revision		Revision as of 10:31, 22 June 2022
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	==Human Cdc34 E2 in complex with CC0651 inhibitor==		==Human Cdc34 E2 in complex with CC0651 inhibitor==
-	<StructureSection load='3rz3' size='340' side='right' caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='3rz3' size='340' side='right'caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3rz3]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. 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>	+	<table><tr><td colspan='2'>[[3rz3]] is a 4 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=3RZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZ3 FirstGlance]. <br>
-	</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>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U94:4,5-DIDEOXY-5-(3,5-DICHLOROBIPHENYL-4-YL)-4-[(METHOXYACETYL)AMINO]-L-ARABINONIC+ACID'>U94</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ob4\|2ob4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ob4\|2ob4]]</div></td></tr>
-	<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 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CDC34, UBCH3, UBE2R1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<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>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
-	<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~~://pdbe.org/3rz3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3rz3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3rz3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3rz3 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=3rz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rz3 OCA], [https://pdbe.org/3rz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rz3 RCSB], [https://www.ebi.ac.uk/pdbsum/3rz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rz3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~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>	+	[[https://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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[~~Ubiquitin~~ conjugating enzyme\|~~Ubiquitin~~ conjugating enzyme]]	+	*[[3D structures of ubiquitin conjugating enzyme\|3D structures of ubiquitin conjugating enzyme]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Ubiquitin--protein ligase]]		[[Category: Ubiquitin--protein ligase]]
	[[Category: Ceccarelli, D F]]		[[Category: Ceccarelli, D F]]

OCA at 19:49, 4 August 2016

2016-08-04T19:49:05Z

←Older revision		Revision as of 19:49, 4 August 2016
Line 1:		Line 1:
		+
	==Human Cdc34 E2 in complex with CC0651 inhibitor==		==Human Cdc34 E2 in complex with CC0651 inhibitor==
	<StructureSection load='3rz3' size='340' side='right' caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='3rz3' size='340' side='right' caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<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>	+	<table><tr><td colspan='2'>[[3rz3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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>
	</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>		</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>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ob4\|2ob4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ob4\|2ob4]]</td></tr>
-	<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>	+	<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 HUMAN])</td></tr>
	<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>		<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>
-	<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>	+	<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://pdbe.org/3rz3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rz3 RCSB], [http://www.ebi.ac.uk/pdbsum/3rz3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rz3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3rz3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Ubiquitin--protein ligase]]		[[Category: Ubiquitin--protein ligase]]
	[[Category: Ceccarelli, D F]]		[[Category: Ceccarelli, D F]]

OCA at 12:33, 25 December 2014

2014-12-25T12:33:46Z

←Older revision		Revision as of 12:33, 25 December 2014
Line 9:		Line 9:
	<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>		<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>
	</table>		</table>
		+	== Function ==
		+	[[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:57, 19 December 2014

2014-12-19T10:57:15Z

←Older revision		Revision as of 10:57, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3rz3\| PDB=3rz3 \| SCENE= }}~~	+	==Human Cdc34 E2 in complex with CC0651 inhibitor==
-	===Human Cdc34 E2 in complex with CC0651 inhibitor===	+	<StructureSection load='3rz3' size='340' side='right' caption='[[3rz3]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21683433}}~~	+	== Structural highlights ==
		+	<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>
		+	</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>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ob4\|2ob4]]</td></tr>
		+	<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>
		+	<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>
		+	<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>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	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.

-	~~==Function==~~	+	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>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:021683433</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Ubiquitin conjugating enzyme\|Ubiquitin conjugating enzyme]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ubiquitin--protein ligase]]		[[Category: Ubiquitin--protein ligase]]
-	[[Category: Ceccarelli, D F.]]	+	[[Category: Ceccarelli, D F]]
-	[[Category: Sicheri, F.]]	+	[[Category: Sicheri, F]]
-	[[Category: Webb, D R.]]	+	[[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]]

OCA at 07:58, 16 May 2013

2013-05-16T07:58:51Z

←Older revision		Revision as of 07:58, 16 May 2013
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-	[[Image:3rz3.jpg\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3rz3", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3rz3\| PDB=3rz3 \| SCENE= }}		{{STRUCTURE_3rz3\| PDB=3rz3 \| SCENE= }}
-
	===Human Cdc34 E2 in complex with CC0651 inhibitor===		===Human Cdc34 E2 in complex with CC0651 inhibitor===
		+	{{ABSTRACT_PUBMED_21683433}}

-		+	==Function==
-	<!--	+	[[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>
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21683433}}, adds~~ the ~~Publication Abstract to~~ the ~~page~~	+
-	(as ~~it appears on PubMed~~ at ~~http:~~/~~/www~~.~~pubmed.gov~~)~~, where 21683433 is~~ the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21683433}}~~	+

	==About this Structure==		==About this Structure==
Line 22:		Line 10:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021683433</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021683433</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ubiquitin--protein ligase]]		[[Category: Ubiquitin--protein ligase]]

OCA at 18:43, 6 July 2011

2011-07-06T18:43:40Z

←Older revision		Revision as of 18:43, 6 July 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3rz3.jpg\|left\|200px]]

-	The ~~entry 3rz3~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3rz3", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3rz3\| PDB=3rz3 \| SCENE= }}

-	~~Authors: Ceccarelli, D.F., Webb, D.R., Sicheri, F.~~	+	===Human Cdc34 E2 in complex with CC0651 inhibitor===

-	~~Description~~: ~~Human Cdc34 E2 in complex~~ with ~~CC0651~~ inhibitor	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21683433}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21683433 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21683433}}
		+
		+	==About this Structure==
		+	[[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].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021683433</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Ubiquitin--protein ligase]]
		+	[[Category: Ceccarelli, D F.]]
		+	[[Category: Sicheri, F.]]
		+	[[Category: Webb, D R.]]
		+	[[Category: E2 domain]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: Ubiquitin conjugating enzyme domain]]

OCA at 04:51, 8 June 2011

2011-06-08T04:51:24Z

←Older revision		Revision as of 04:51, 8 June 2011
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3rz3 is ON HOLD	+	The entry 3rz3 is ON HOLD until Paper Publication

	Authors: Ceccarelli, D.F., Webb, D.R., Sicheri, F.		Authors: Ceccarelli, D.F., Webb, D.R., Sicheri, F.

	Description: Human Cdc34 E2 in complex with CC0651 inhibitor		Description: Human Cdc34 E2 in complex with CC0651 inhibitor

OCA: Protected "3rz3" [edit=sysop:move=sysop]

2011-05-18T05:19:56Z

Protected "3rz3" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:19, 18 May 2011

OCA: New page: '''Unreleased structure''' The entry 3rz3 is ON HOLD Authors: Ceccarelli, D.F., Webb, D.R., Sicheri, F. Description: Human Cdc34 E2 in complex with CC0651 inhibitor

2011-05-18T05:19:55Z

New page: '''Unreleased structure''' The entry 3rz3 is ON HOLD Authors: Ceccarelli, D.F., Webb, D.R., Sicheri, F. Description: Human Cdc34 E2 in complex with CC0651 inhibitor

New page

'''Unreleased structure'''

The entry 3rz3 is ON HOLD

Authors: Ceccarelli, D.F., Webb, D.R., Sicheri, F.

Description: Human Cdc34 E2 in complex with CC0651 inhibitor