5fqd - Revision history

OCA at 13:18, 26 July 2023

OCA — Wed, 26 Jul 2023 13:18:33 GMT

←Older revision		Revision as of 13:18, 26 July 2023
Line 3:		Line 3:
	<StructureSection load='5fqd' size='340' side='right'caption='[[5fqd]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='5fqd' size='340' side='right'caption='[[5fqd]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5fqd]] 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=5FQD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5FQD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5fqd]] is a 6 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=5FQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FQD FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=LVY:S~~-~~LENALIDOMIDE'>LVY</scene>~~, ~~<scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.45Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LVY:S-LENALIDOMIDE'>LVY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5fqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fqd OCA], [~~http~~://pdbe.org/5fqd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5fqd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5fqd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5fqd 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=5fqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fqd OCA], [https://pdbe.org/5fqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fqd RCSB], [https://www.ebi.ac.uk/pdbsum/5fqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fqd ProSAT]</span></td></tr>
	</table>		</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 ==		== 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/KC1A_HUMAN KC1A_HUMAN]] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).<ref>PMID:11955436</ref> <ref>PMID:1409656</ref> <ref>PMID:18305108</ref> <ref>PMID:23902688</ref> [[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>	+	[https://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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 21:

	==See Also==		==See Also==
-	*[[Casein kinase\|Casein kinase]]	+	*[[Casein kinase 3D structures\|Casein kinase 3D structures]]
	*[[DNA damage-binding protein\|DNA damage-binding protein]]		*[[DNA damage-binding protein\|DNA damage-binding protein]]
-	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]	+	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Ubiquitin--protein ligase]]~~	+	[[Category: Fischer ES]]
-	[[Category: Fischer~~, E S~~]]	+	[[Category: Petzold G]]
-	[[Category: Petzold, G]]	+	[[Category: Thoma NH]]
-	[[Category: Thoma~~, N H]]~~	+
-	~~[[Category: Dna binding]]~~	+
-	~~[[Category: Ligase~~]]	+

OCA at 07:55, 3 April 2019

OCA — Wed, 03 Apr 2019 07:55:26 GMT

←Older revision		Revision as of 07:55, 3 April 2019
Line 1:		Line 1:

	==Structural basis of Lenalidomide induced CK1a degradation by the crl4crbn ubiquitin ligase==		==Structural basis of Lenalidomide induced CK1a degradation by the crl4crbn ubiquitin ligase==
-	<StructureSection load='5fqd' size='340' side='right' caption='[[5fqd]], [[Resolution\|resolution]] 2.45Å' scene=''>	+	<StructureSection load='5fqd' size='340' side='right'caption='[[5fqd]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5fqd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FQD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5fqd]] 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=5FQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FQD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LVY:S-LENALIDOMIDE'>LVY</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=LVY:S-LENALIDOMIDE'>LVY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5fqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fqd OCA], [http://pdbe.org/5fqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fqd RCSB], [http://www.ebi.ac.uk/pdbsum/5fqd 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=5fqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fqd OCA], [http://pdbe.org/5fqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fqd RCSB], [http://www.ebi.ac.uk/pdbsum/5fqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fqd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5fqd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5fqd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Casein kinase\|Casein kinase]]
		+	*[[DNA damage-binding protein\|DNA damage-binding protein]]
		+	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Ubiquitin--protein ligase]]		[[Category: Ubiquitin--protein ligase]]
	[[Category: Fischer, E S]]		[[Category: Fischer, E S]]

OCA at 19:49, 9 March 2016

OCA — Wed, 09 Mar 2016 19:49:45 GMT

←Older revision		Revision as of 19:49, 9 March 2016
Line 12:		Line 12:
	== 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/KC1A_HUMAN KC1A_HUMAN]] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).<ref>PMID:11955436</ref> <ref>PMID:1409656</ref> <ref>PMID:18305108</ref> <ref>PMID:23902688</ref> [[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/KC1A_HUMAN KC1A_HUMAN]] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).<ref>PMID:11955436</ref> <ref>PMID:1409656</ref> <ref>PMID:18305108</ref> <ref>PMID:23902688</ref> [[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 ==
		+	Thalidomide and its derivatives, lenalidomide and pomalidomide, are immune modulatory drugs (IMiDs) used in the treatment of haematologic malignancies. IMiDs bind CRBN, the substrate receptor of the CUL4-RBX1-DDB1-CRBN (also known as CRL4CRBN) E3 ubiquitin ligase, and inhibit ubiquitination of endogenous CRL4CRBN substrates. Unexpectedly, IMiDs also repurpose the ligase to target new proteins for degradation. Lenalidomide induces degradation of the lymphoid transcription factors Ikaros and Aiolos (also known as IKZF1 and IKZF3), and casein kinase 1alpha (CK1alpha), which contributes to its clinical efficacy in the treatment of multiple myeloma and 5q-deletion associated myelodysplastic syndrome (del(5q) MDS), respectively. How lenalidomide alters the specificity of the ligase to degrade these proteins remains elusive. Here we present the 2.45 A crystal structure of DDB1-CRBN bound to lenalidomide and CK1alpha. CRBN and lenalidomide jointly provide the binding interface for a CK1alpha beta-hairpin-loop located in the kinase N-lobe. We show that CK1alpha binding to CRL4CRBN is strictly dependent on the presence of an IMiD. Binding of IKZF1 to CRBN similarly requires the compound and both, IKZF1 and CK1alpha, use a related binding mode. Our study provides a mechanistic explanation for the selective efficacy of lenalidomide in del(5q) MDS therapy. We anticipate that high-affinity protein-protein interactions induced by small molecules will provide opportunities for drug development, particularly for targeted protein degradation.
		+
		+	Structural basis of lenalidomide-induced CK1alpha degradation by the CRL4 ubiquitin ligase.,Petzold G, Fischer ES, Thoma NH Nature. 2016 Feb 24. doi: 10.1038/nature16979. PMID:26909574<ref>PMID:26909574</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5fqd" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:21, 26 February 2016

OCA — Fri, 26 Feb 2016 18:21:38 GMT

←Older revision		Revision as of 18:21, 26 February 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5fqd is ~~ON HOLD until Paper Publication~~	+	==Structural basis of Lenalidomide induced CK1a degradation by the crl4crbn ubiquitin ligase==
-		+	<StructureSection load='5fqd' size='340' side='right' caption='[[5fqd]], [[Resolution\|resolution]] 2.45Å' scene=''>
-	~~Authors~~: ~~Petzold~~, G., ~~Fischer~~, E.S., ~~Thoma~~, N.H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5fqd]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FQD FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LVY:S-LENALIDOMIDE'>LVY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5fqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fqd OCA], [http://pdbe.org/5fqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fqd RCSB], [http://www.ebi.ac.uk/pdbsum/5fqd PDBsum]</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/KC1A_HUMAN KC1A_HUMAN]] Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).<ref>PMID:11955436</ref> <ref>PMID:1409656</ref> <ref>PMID:18305108</ref> <ref>PMID:23902688</ref> [[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: Ubiquitin--protein ligase]]
		+	[[Category: Fischer, E S]]
	[[Category: Petzold, G]]		[[Category: Petzold, G]]
-	[[Category: ~~Fischer~~, ~~E.S~~]]	+	[[Category: Thoma, N H]]
-	[[Category: ~~Thoma, N.H~~]]	+	[[Category: Dna binding]]
		+	[[Category: Ligase]]

OCA at 18:32, 13 January 2016

OCA — Wed, 13 Jan 2016 18:32:08 GMT

←Older revision		Revision as of 18:32, 13 January 2016
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5fqd is ON HOLD	+	The entry 5fqd is ON HOLD until Paper Publication

	Authors: Petzold, G., Fischer, E.S., Thoma, N.H.		Authors: Petzold, G., Fischer, E.S., Thoma, N.H.

OCA at 18:16, 30 December 2015

OCA — Wed, 30 Dec 2015 18:16:58 GMT

←Older revision		Revision as of 18:16, 30 December 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5fqd is ON HOLD ~~until sometime in the future~~	+	The entry 5fqd is ON HOLD

	Authors: Petzold, G., Fischer, E.S., Thoma, N.H.		Authors: Petzold, G., Fischer, E.S., Thoma, N.H.

-	Description: ~~NA given upon final title of the paper~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Petzold, G]]		[[Category: Petzold, G]]
	[[Category: Fischer, E.S]]		[[Category: Fischer, E.S]]
	[[Category: Thoma, N.H]]		[[Category: Thoma, N.H]]

OCA: Protected "5fqd" [edit=sysop:move=sysop]

OCA — Wed, 16 Dec 2015 13:02:04 GMT

Protected "5fqd" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:02, 16 December 2015

OCA: New page: '''Unreleased structure''' The entry 5fqd is ON HOLD until sometime in the future Authors: Petzold, G., Fischer, E.S., Thoma, N.H. Description: NA given upon final title of the paper [...

OCA — Wed, 16 Dec 2015 13:02:02 GMT

New page: '''Unreleased structure''' The entry 5fqd is ON HOLD until sometime in the future Authors: Petzold, G., Fischer, E.S., Thoma, N.H. Description: NA given upon final title of the paper [...

New page

'''Unreleased structure'''

The entry 5fqd is ON HOLD until sometime in the future

Authors: Petzold, G., Fischer, E.S., Thoma, N.H.

Description: NA given upon final title of the paper
[[Category: Unreleased Structures]]
[[Category: Petzold, G]]
[[Category: Fischer, E.S]]
[[Category: Thoma, N.H]]