6h0g - Revision history

OCA at 06:50, 17 April 2019

OCA — Wed, 17 Apr 2019 06:50:44 GMT

←Older revision		Revision as of 06:50, 17 April 2019
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	==Structure of the DDB1-CRBN-pomalidomide complex bound to ZNF692(ZF4)==		==Structure of the DDB1-CRBN-pomalidomide complex bound to ZNF692(ZF4)==
-	<StructureSection load='6h0g' size='340' side='right' caption='[[6h0g]], [[Resolution\|resolution]] 4.25Å' scene=''>	+	<StructureSection load='6h0g' size='340' side='right'caption='[[6h0g]], [[Resolution\|resolution]] 4.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6h0g]] is a 6 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=6H0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H0G FirstGlance]. <br>		<table><tr><td colspan='2'>[[6h0g]] is a 6 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=6H0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H0G FirstGlance]. <br>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bunker, R D]]		[[Category: Bunker, R D]]
	[[Category: Petzold, G]]		[[Category: Petzold, G]]

OCA at 09:04, 14 November 2018

OCA — Wed, 14 Nov 2018 09:04:13 GMT

←Older revision		Revision as of 09:04, 14 November 2018
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	<StructureSection load='6h0g' size='340' side='right' caption='[[6h0g]], [[Resolution\|resolution]] 4.25Å' scene=''>		<StructureSection load='6h0g' size='340' side='right' caption='[[6h0g]], [[Resolution\|resolution]] 4.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6h0g]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H0G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6h0g]] is a 6 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=6H0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H0G FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y70:S-POMALIDOMIDE'>Y70</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y70:S-POMALIDOMIDE'>Y70</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6h0f\|6h0f]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6h0f\|6h0f]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DDB1, XAP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CRBN, AD-006 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ZNF692 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6h0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h0g OCA], [http://pdbe.org/6h0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h0g RCSB], [http://www.ebi.ac.uk/pdbsum/6h0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h0g ProSAT]</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=6h0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h0g OCA], [http://pdbe.org/6h0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h0g RCSB], [http://www.ebi.ac.uk/pdbsum/6h0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h0g ProSAT]</span></td></tr>
	</table>		</table>
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN]] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</ref> [[http://www.uniprot.org/uniprot/ZN692_HUMAN ZN692_HUMAN]] May be involved in transcriptional regulation. [[http://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN]] Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1.<ref>PMID:18414909</ref> <ref>PMID:20223979</ref>		[[http://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN]] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</ref> [[http://www.uniprot.org/uniprot/ZN692_HUMAN ZN692_HUMAN]] May be involved in transcriptional regulation. [[http://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN]] Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1.<ref>PMID:18414909</ref> <ref>PMID:20223979</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The small molecules thalidomide, lenalidomide, and pomalidomide induce the ubiquitination and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by recruiting a Cys2-His2 (C2H2) zinc finger domain to Cereblon (CRBN), the substrate receptor of the CRL4(CRBN) E3 ubiquitin ligase. We screened the human C2H2 zinc finger proteome for degradation in the presence of thalidomide analogs, identifying 11 zinc finger degrons. Structural and functional characterization of the C2H2 zinc finger degrons demonstrates how diverse zinc finger domains bind the permissive drug-CRBN interface. Computational zinc finger docking and biochemical analysis predict that more than 150 zinc fingers bind the drug-CRBN complex in vitro, and we show that selective zinc finger degradation can be achieved through compound modifications. Our results provide a rationale for therapeutically targeting transcription factors that were previously considered undruggable.
		+
		+	Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN.,Sievers QL, Petzold G, Bunker RD, Renneville A, Slabicki M, Liddicoat BJ, Abdulrahman W, Mikkelsen T, Ebert BL, Thoma NH Science. 2018 Nov 2;362(6414). pii: 362/6414/eaat0572. doi:, 10.1126/science.aat0572. PMID:30385546<ref>PMID:30385546</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6h0g" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Bunker, R D]]		[[Category: Bunker, R D]]
	[[Category: Petzold, G]]		[[Category: Petzold, G]]

OCA at 12:20, 7 November 2018

OCA — Wed, 07 Nov 2018 12:20:45 GMT

←Older revision		Revision as of 12:20, 7 November 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6h0g is ~~ON HOLD until Paper Publication~~	+	==Structure of the DDB1-CRBN-pomalidomide complex bound to ZNF692(ZF4)==
-		+	<StructureSection load='6h0g' size='340' side='right' caption='[[6h0g]], [[Resolution\|resolution]] 4.25Å' scene=''>
-	~~Authors~~: ~~Bunker~~, R.D., ~~Petzold~~, G., ~~Thoma~~, N.H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6h0g]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H0G FirstGlance]. <br>
-	~~Description~~: ~~Structure~~ of the DDB1-~~CRBN~~-~~pomalidomide~~ complex ~~bound~~ to ~~ZNF692~~(~~ZF4~~)	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y70:S-POMALIDOMIDE'>Y70</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6h0f\|6h0f]]</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=6h0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h0g OCA], [http://pdbe.org/6h0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h0g RCSB], [http://www.ebi.ac.uk/pdbsum/6h0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h0g ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN]] Autosomal recessive nonsyndromic intellectual deficit;Distal monosomy 3p. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN]] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</ref> [[http://www.uniprot.org/uniprot/ZN692_HUMAN ZN692_HUMAN]] May be involved in transcriptional regulation. [[http://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN]] Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1.<ref>PMID:18414909</ref> <ref>PMID:20223979</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bunker, R D]]
	[[Category: Petzold, G]]		[[Category: Petzold, G]]
-	[[Category: ~~Bunker~~, ~~R.D~~]]	+	[[Category: Thoma, N H]]
-	[[Category: ~~Thoma, N.H~~]]	+	[[Category: Drug mediated protein-interaction]]
		+	[[Category: E3 ubiquitin ligase]]
		+	[[Category: Signaling protein]]
		+	[[Category: Targeted protein degradation]]

OCA at 05:07, 31 October 2018

OCA — Wed, 31 Oct 2018 05:07:27 GMT

←Older revision		Revision as of 05:07, 31 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6h0g is ON HOLD	+	The entry 6h0g is ON HOLD until Paper Publication

	Authors: Bunker, R.D., Petzold, G., Thoma, N.H.		Authors: Bunker, R.D., Petzold, G., Thoma, N.H.

OCA at 17:12, 1 August 2018

OCA — Wed, 01 Aug 2018 17:12:09 GMT

←Older revision		Revision as of 17:12, 1 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6h0g is ON HOLD ~~until sometime in the future~~	+	The entry 6h0g is ON HOLD

	Authors: Bunker, R.D., Petzold, G., Thoma, N.H.		Authors: Bunker, R.D., Petzold, G., Thoma, N.H.

OCA: Protected "6h0g" [edit=sysop:move=sysop]

OCA — Wed, 18 Jul 2018 05:47:59 GMT

Protected "6h0g" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:47, 18 July 2018

OCA: New page: '''Unreleased structure''' The entry 6h0g is ON HOLD until sometime in the future Authors: Bunker, R.D., Petzold, G., Thoma, N.H. Description: Structure of the DDB1-CRBN-pomalidomide c...

OCA — Wed, 18 Jul 2018 05:47:57 GMT

New page: '''Unreleased structure''' The entry 6h0g is ON HOLD until sometime in the future Authors: Bunker, R.D., Petzold, G., Thoma, N.H. Description: Structure of the DDB1-CRBN-pomalidomide c...

New page

'''Unreleased structure'''

The entry 6h0g is ON HOLD until sometime in the future

Authors: Bunker, R.D., Petzold, G., Thoma, N.H.

Description: Structure of the DDB1-CRBN-pomalidomide complex bound to ZNF692(ZF4)
[[Category: Unreleased Structures]]
[[Category: Petzold, G]]
[[Category: Bunker, R.D]]
[[Category: Thoma, N.H]]