4w9e - Revision history

OCA at 10:41, 10 January 2024

2024-01-10T10:41:20Z

←Older revision		Revision as of 10:41, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4w9e]] is a 12 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=4W9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4W9E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4w9e]] is a 12 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=4W9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4W9E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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]] 2.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [https://pdbe.org/4w9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [https://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e 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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [https://pdbe.org/4w9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [https://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:58, 7 April 2023

2023-04-07T06:58:16Z

←Older revision		Revision as of 06:58, 7 April 2023
Line 3:		Line 3:
	<StructureSection load='4w9e' size='340' side='right'caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4w9e' size='340' side='right'caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4w9e]] is a 12 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=4W9E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4W9E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4w9e]] is a 12 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=4W9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4W9E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>~~</td></tr>~~	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [https://pdbe.org/4w9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [https://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TCEB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCEB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VHL ([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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [~~http~~://pdbe.org/4w9e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:[http://omim.org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref> <ref>PMID:8493574</ref> <ref>PMID:7987306</ref> <ref>PMID:7728151</ref> <ref>PMID:8634692</ref> <ref>PMID:8592333</ref> <ref>PMID:8825918</ref> <ref>PMID:8730290</ref> <ref>PMID:8956040</ref> <ref>PMID:9452032</ref> <ref>PMID:9452106</ref> <ref>PMID:10627136</ref> <ref>PMID:9829911</ref> <ref>PMID:9829912</ref> [:]<ref>PMID:10533030</ref> <ref>PMID:10408776</ref> <ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:[http://omim.org/entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.<ref>PMID:12844285</ref> <ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:11986208</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> [[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.<ref>PMID:9751722</ref> <ref>PMID:10944113</ref> <ref>PMID:19584355</ref> [[http://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>	+	[https://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 20:

	==See Also==		==See Also==
-	*[[Elongation factor\|Elongation factor]]	+	*[[Elongation factor 3D structures\|Elongation factor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ciulli, A]]	+	[[Category: Ciulli A]]
-	[[Category: Gadd~~, M S~~]]	+	[[Category: Gadd MS]]
-	[[Category: Galdeano, C]]	+	[[Category: Galdeano C]]
-	~~[[Category: Molle, I van~~]]	+	[[Category: Soares P]]
-	[[Category: Soares, P]]	+	[[Category: Van Molle I]]
-	[[Category: ~~Hypoxia inducible factor]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Protein complex]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Ubiquitin ligase~~]]	+

OCA at 08:04, 23 May 2019

2019-05-23T08:04:43Z

←Older revision		Revision as of 08:04, 23 May 2019
Line 1:		Line 1:

	==pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)==		==pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)==
-	<StructureSection load='4w9e' size='340' side='right' caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='4w9e' size='340' side='right'caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4w9e]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4W9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4W9E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4w9e]] is a 12 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=4W9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4W9E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TCEB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCEB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VHL ([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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://pdbe.org/4w9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e 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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://pdbe.org/4w9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4w9e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4w9e" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Elongation factor\|Elongation factor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Ciulli, A]]		[[Category: Ciulli, A]]
	[[Category: Gadd, M S]]		[[Category: Gadd, M S]]

OCA at 13:24, 11 August 2016

2016-08-11T13:24:40Z

←Older revision		Revision as of 13:24, 11 August 2016
Line 1:		Line 1:
		+
	==pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)==		==pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)==
	<StructureSection load='4w9e' size='340' side='right' caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='4w9e' size='340' side='right' caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e 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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://pdbe.org/4w9e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4w9e ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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 4w9e" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:55, 25 January 2015

2015-01-25T10:55:04Z

←Older revision		Revision as of 10:55, 25 January 2015
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Ciulli, A.]]	+	[[Category: Ciulli, A]]
-	[[Category: Gadd, M S.]]	+	[[Category: Gadd, M S]]
-	[[Category: Galdeano, C.]]	+	[[Category: Galdeano, C]]
-	[[Category: Molle, I van.]]	+	[[Category: Molle, I van]]
-	[[Category: Soares, P.]]	+	[[Category: Soares, P]]
	[[Category: Hypoxia inducible factor]]		[[Category: Hypoxia inducible factor]]
	[[Category: Ligase]]		[[Category: Ligase]]

OCA at 07:01, 5 November 2014

2014-11-05T07:01:23Z

←Older revision		Revision as of 07:01, 5 November 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4w9e]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4W9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4W9E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4w9e]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4W9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4W9E FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e 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=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:[http://omim.org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref> <ref>PMID:8493574</ref> <ref>PMID:7987306</ref> <ref>PMID:7728151</ref> <ref>PMID:8634692</ref> <ref>PMID:8592333</ref> <ref>PMID:8825918</ref> <ref>PMID:8730290</ref> <ref>PMID:8956040</ref> <ref>PMID:9452032</ref> <ref>PMID:9452106</ref> <ref>PMID:10627136</ref> <ref>PMID:9829911</ref> <ref>PMID:9829912</ref> [:]<ref>PMID:10533030</ref> <ref>PMID:10408776</ref> <ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:[http://omim.org/entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.<ref>PMID:12844285</ref> <ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:11986208</ref>		[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:[http://omim.org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref> <ref>PMID:8493574</ref> <ref>PMID:7987306</ref> <ref>PMID:7728151</ref> <ref>PMID:8634692</ref> <ref>PMID:8592333</ref> <ref>PMID:8825918</ref> <ref>PMID:8730290</ref> <ref>PMID:8956040</ref> <ref>PMID:9452032</ref> <ref>PMID:9452106</ref> <ref>PMID:10627136</ref> <ref>PMID:9829911</ref> <ref>PMID:9829912</ref> [:]<ref>PMID:10533030</ref> <ref>PMID:10408776</ref> <ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:[http://omim.org/entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.<ref>PMID:12844285</ref> <ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:11986208</ref>

OCA at 09:58, 10 September 2014

2014-09-10T09:58:40Z

←Older revision		Revision as of 09:58, 10 September 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)==
		+	<StructureSection load='4w9e' size='340' side='right' caption='[[4w9e]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4w9e]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4W9E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4W9E FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JT:(4R)-1-(3,3-DIMETHYLBUTANOYL)-4-HYDROXY-N-[4-(1,3-THIAZOL-5-YL)BENZYL]-L-PROLINAMIDE'>3JT</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4w9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4w9e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4w9e RCSB], [http://www.ebi.ac.uk/pdbsum/4w9e PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:[http://omim.org/entry/171300 171300]]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:[http://omim.org/entry/193300 193300]]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years.<ref>PMID:10635329</ref> <ref>PMID:8493574</ref> <ref>PMID:7987306</ref> <ref>PMID:7728151</ref> <ref>PMID:8634692</ref> <ref>PMID:8592333</ref> <ref>PMID:8825918</ref> <ref>PMID:8730290</ref> <ref>PMID:8956040</ref> <ref>PMID:9452032</ref> <ref>PMID:9452106</ref> <ref>PMID:10627136</ref> <ref>PMID:9829911</ref> <ref>PMID:9829912</ref> [:]<ref>PMID:10533030</ref> <ref>PMID:10408776</ref> <ref>PMID:16502427</ref> Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:[http://omim.org/entry/263400 263400]]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.<ref>PMID:12844285</ref> <ref>PMID:12393546</ref> Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:[http://omim.org/entry/144700 144700]]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:11986208</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> [[http://www.uniprot.org/uniprot/VHL_HUMAN VHL_HUMAN]] Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.<ref>PMID:9751722</ref> <ref>PMID:10944113</ref> <ref>PMID:19584355</ref> [[http://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however the development of small molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1alpha for degradation. We recently reported inhibitors of the pVHL:HIF-1alpha interaction that however exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities.

-	~~The entry 4w9e is ON HOLD until Paper Publication~~	+	Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with In Vitro Nanomolar Affinities.,Galdeano C, Gadd MS, Soares P, Scaffidi S, Van Molle I, Birced I, Hewitt S, Dias DM, Ciulli A J Med Chem. 2014 Aug 28. PMID:25166285<ref>PMID:25166285</ref>

-	~~Authors: Gadd~~, M.S., ~~Soares, P~~., Galdeano, C.~~, van~~ Molle, I., ~~Ciulli, A~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~pVHL~~:~~EloB:EloC in~~ complex ~~with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Ciulli, A.]]
		+	[[Category: Gadd, M S.]]
		+	[[Category: Galdeano, C.]]
		+	[[Category: Molle, I van.]]
		+	[[Category: Soares, P.]]
		+	[[Category: Hypoxia inducible factor]]
		+	[[Category: Ligase]]
		+	[[Category: Protein complex]]
		+	[[Category: Transcription]]
		+	[[Category: Ubiquitin ligase]]

OCA: Protected "4w9e" [edit=sysop:move=sysop]

2014-09-04T04:50:09Z

Protected "4w9e" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:50, 4 September 2014

OCA: New page: '''Unreleased structure''' The entry 4w9e is ON HOLD until Paper Publication Authors: Gadd, M.S., Soares, P., Galdeano, C., van Molle, I., Ciulli, A. Description: pVHL:EloB:EloC in com...

2014-09-04T04:50:07Z

New page: '''Unreleased structure''' The entry 4w9e is ON HOLD until Paper Publication Authors: Gadd, M.S., Soares, P., Galdeano, C., van Molle, I., Ciulli, A. Description: pVHL:EloB:EloC in com...

New page

'''Unreleased structure'''

The entry 4w9e is ON HOLD until Paper Publication

Authors: Gadd, M.S., Soares, P., Galdeano, C., van Molle, I., Ciulli, A.

Description: pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)