6fmj - Revision history

OCA at 06:33, 20 June 2018

OCA — Wed, 20 Jun 2018 06:33:17 GMT

←Older revision		Revision as of 06:33, 20 June 2018
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	</div>		</div>
	<div class="pdbe-citations 6fmj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6fmj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Elongation factor\|Elongation factor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:08, 25 April 2018

OCA — Wed, 25 Apr 2018 06:08:58 GMT

←Older revision		Revision as of 06:08, 25 April 2018
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	<StructureSection load='6fmj' size='340' side='right' caption='[[6fmj]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='6fmj' size='340' side='right' caption='[[6fmj]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6fmj]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FMJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6fmj]] 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=6FMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FMJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DV5:(2~{S},4~{R})-1-[(2~{S})-2-acetamidopropanethioyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>DV5</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DV5:(2~{S},4~{R})-1-[(2~{S})-2-acetamidopropanethioyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>DV5</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">ELOB, TCEB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ELOC, 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=6fmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fmj OCA], [http://pdbe.org/6fmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fmj RCSB], [http://www.ebi.ac.uk/pdbsum/6fmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fmj 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=6fmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fmj OCA], [http://pdbe.org/6fmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fmj RCSB], [http://www.ebi.ac.uk/pdbsum/6fmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fmj ProSAT]</span></td></tr>
	</table>		</table>
Line 12:		Line 13:
	== 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>		[[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 ==
		+	Thioamide substitution influences hydrogen bond and n --> pi( ) interactions involved in the conformational stability of protein secondary structures and oligopeptides. Hydroxyproline is the key recognition element of small molecules targeting the von Hippel-Lindau (VHL) E3 ligase, which are of interest as probes of hypoxia signaling and ligands for PROTAC conjugation. We hypothesized that VHL ligands could be a privileged model system to evaluate the contribution of these interactions to protein:ligand complex formation. Herein we report the synthesis of VHL ligands bearing thioamide substitutions at the central hydroxyproline moiety, and characterize their binding by fluorescence polarization, isothermal titration calorimetry, X-ray crystallography and molecular modeling. In spite of a conserved binding mode, the substitution pattern had a pronounced impact on the ligand affinities. Together the results underscore the role of hydrogen bond and n --> pi( ) interactions in fine tuning hydroxyproline recognition by VHL.
		+
		+	Thioamide substitution to probe the hydroxyproline recognition of VHL ligands.,Soares P, Lucas X, Ciulli A Bioorg Med Chem. 2018 Mar 23. pii: S0968-0896(18)30348-1. doi:, 10.1016/j.bmc.2018.03.034. PMID:29650462<ref>PMID:29650462</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6fmj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Ciulli, A]]		[[Category: Ciulli, A]]
	[[Category: Lucas, X]]		[[Category: Lucas, X]]

OCA at 13:57, 11 April 2018

OCA — Wed, 11 Apr 2018 13:57:52 GMT

←Older revision		Revision as of 13:57, 11 April 2018
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-	'''Unreleased structure'''

-	The entry ~~6fmj~~ is ~~ON HOLD~~	+	==pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-2-Acetamidopropanethioyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl) benzyl)pyrrolidine-2-carboxamide (ligand 3)==
-		+	<StructureSection load='6fmj' size='340' side='right' caption='[[6fmj]], [[Resolution\|resolution]] 2.45Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6fmj]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FMJ FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DV5:(2~{S},4~{R})-1-[(2~{S})-2-acetamidopropanethioyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>DV5</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=6fmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fmj OCA], [http://pdbe.org/6fmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fmj RCSB], [http://www.ebi.ac.uk/pdbsum/6fmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fmj ProSAT]</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Ciulli, A]]
		+	[[Category: Lucas, X]]
		+	[[Category: Soares, P]]
		+	[[Category: Hypoxia inducible factor]]
		+	[[Category: Ligase]]
		+	[[Category: Protein complex]]
		+	[[Category: Ubiquitin ligase]]

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

OCA — Wed, 07 Feb 2018 05:19:32 GMT

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

←Older revision

Revision as of 05:19, 7 February 2018

OCA: New page: '''Unreleased structure''' The entry 6fmj is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 07 Feb 2018 05:19:31 GMT

New page: '''Unreleased structure''' The entry 6fmj is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6fmj is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]