3cs4 - Revision history

OCA at 09:37, 21 February 2024

2024-02-21T09:37:49Z

← Older revision		Revision as of 09:37, 21 February 2024
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	<StructureSection load='3cs4' size='340' side='right'caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cs4' size='340' side='right'caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cs4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cs4]] is a 1 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=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</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]] 2Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cs6\|3cs6]]</div></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [https://pdbe.org/3cs4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [https://www.ebi.ac.uk/pdbsum/3cs4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cs4 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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [https://pdbe.org/3cs4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [https://www.ebi.ac.uk/pdbsum/3cs4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cs4 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[https://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>		[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[https://omim.org/entry/277440 277440]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>		[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cs4 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cs4 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Vitamin D nuclear receptor (VDR), a ligand-dependent transcriptional regulator, is an important target for multiple clinical applications, such as osteoporosis and cancer. Since exacerbated increase of calcium serum level is currently associated with VDR ligands action, superagonists with low calcium serum levels have been developed. Based on the crystal structures of human VDR (hVDR) bound to 1alpha,25-dihydroxyvitamin D(3) and superagonists-notably, KH1060-we designed a superagonist ligand. In order to optimize the aliphatic side chain conformation with a subsequent entropy benefit, we incorporated an oxolane ring and generated two stereo diasteromers, AMCR277A and AMCR277B. Only AMCR277A exhibits superagonist activity in vitro, but is as calcemic in vivo as the natural ligand. The crystal structures of the complexes between the ligand binding domain of hVDR and these ligands provide a rational approach to the design of more potent superagonist ligands for potential clinical application.

	Structure-based design of a superagonist ligand for the vitamin D nuclear receptor.,Hourai S, Rodrigues LC, Antony P, Reina-San-Martin B, Ciesielski F, Magnier BC, Schoonjans K, Mourino A, Rochel N, Moras D Chem Biol. 2008 Apr;15(4):383-92. PMID:18420145<ref>PMID:18420145</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3cs4" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Antony, P]]		[[Category: Antony P]]
	[[Category: Ciesielski, F]]		[[Category: Ciesielski F]]
	[[Category: Hourai, S]]		[[Category: Hourai S]]
	[[Category: Magnier~~, B C~~]]		[[Category: Magnier BC]]
	[[Category: Moras, D]]		[[Category: Moras D]]
	[[Category: Mourino, A]]		[[Category: Mourino A]]
	[[Category: Reina-San-Martin, B]]		[[Category: Reina-San-Martin B]]
	[[Category: Rochel, N]]		[[Category: Rochel N]]
	[[Category: Rodriguez~~, L C~~]]		[[Category: Rodriguez LC]]
	[[Category: Schoonjans, K]]		[[Category: Schoonjans K]]
	~~[[Category: Disease mutation]]~~
	~~[[Category: Dna-binding]]~~
	~~[[Category: Gene regulation]]~~
	~~[[Category: Metal-binding]]~~
	~~[[Category: Nucleus]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Polymorphism]]~~
	~~[[Category: Receptor]]~~
	~~[[Category: Superagonist]]~~
	~~[[Category: Transcription]]~~
	~~[[Category: Transcription regulation]]~~
	~~[[Category: Vdr]]~~
	~~[[Category: Zinc]]~~
	~~[[Category: Zinc-finger~~]]

OCA at 07:43, 2 February 2022

2022-02-02T07:43:14Z

← Older revision		Revision as of 07:43, 2 February 2022
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	==Structure-based design of a superagonist ligand for the vitamin D nuclear receptor==		==Structure-based design of a superagonist ligand for the vitamin D nuclear receptor==
	<StructureSection load='3cs4' size='340' side='right' caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cs4' size='340' side='right'caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cs4]] is a 1 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=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cs4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cs6\|3cs6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3cs6\|3cs6]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([https://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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [~~http~~://pdbe.org/3cs4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3cs4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3cs4 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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [https://pdbe.org/3cs4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [https://www.ebi.ac.uk/pdbsum/3cs4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cs4 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[~~http~~://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>		[[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[https://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>		[[https://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
	*[[Sandbox vdr\|Sandbox vdr]]		*[[Sandbox vdr\|Sandbox vdr]]
	*[[Vitamin D receptor\|Vitamin D receptor]]		*[[Vitamin D receptor 3D structures\|Vitamin D receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Antony, P]]		[[Category: Antony, P]]
	[[Category: Ciesielski, F]]		[[Category: Ciesielski, F]]

OCA at 13:12, 7 November 2018

2018-11-07T13:12:53Z

← Older revision		Revision as of 13:12, 7 November 2018
Line 1:		Line 1:

	==Structure-based design of a superagonist ligand for the vitamin D nuclear receptor==		==Structure-based design of a superagonist ligand for the vitamin D nuclear receptor==
	<StructureSection load='3cs4' size='340' side='right' caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cs4' size='340' side='right' caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cs6\|3cs6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cs6\|3cs6]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [http://pdbe.org/3cs4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [http://www.ebi.ac.uk/pdbsum/3cs4 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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [http://pdbe.org/3cs4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [http://www.ebi.ac.uk/pdbsum/3cs4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cs4 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cs/3cs4_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cs/3cs4_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
			[[Category: Polymorphism]]
	[[Category: Receptor]]		[[Category: Receptor]]
	[[Category: Superagonist]]		[[Category: Superagonist]]
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	[[Category: Transcription regulation]]		[[Category: Transcription regulation]]
	[[Category: Vdr]]		[[Category: Vdr]]
			[[Category: Zinc]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

OCA at 00:28, 9 February 2016

2016-02-09T00:28:09Z

← Older revision		Revision as of 00:28, 9 February 2016
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	<StructureSection load='3cs4' size='340' side='right' caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='3cs4' size='340' side='right' caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3cs4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3cs4]] is a 1 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=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cs6\|3cs6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cs6\|3cs6]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [http://www.ebi.ac.uk/pdbsum/3cs4 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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [http://pdbe.org/3cs4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [http://www.ebi.ac.uk/pdbsum/3cs4 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cs4 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 30:
	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 3cs4" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Antony, P]]		[[Category: Antony, P]]
	[[Category: Ciesielski, F]]		[[Category: Ciesielski, F]]

OCA at 08:52, 20 January 2015

2015-01-20T08:52:34Z

← Older revision		Revision as of 08:52, 20 January 2015
Line 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Antony, P.]]		[[Category: Antony, P]]
	[[Category: Ciesielski, F.]]		[[Category: Ciesielski, F]]
	[[Category: Hourai, S.]]		[[Category: Hourai, S]]
	[[Category: Magnier, B C.]]		[[Category: Magnier, B C]]
	[[Category: Moras, D.]]		[[Category: Moras, D]]
	[[Category: Mourino, A.]]		[[Category: Mourino, A]]
	[[Category: Reina-San-Martin, B.]]		[[Category: Reina-San-Martin, B]]
	[[Category: Rochel, N.]]		[[Category: Rochel, N]]
	[[Category: Rodriguez, L C.]]		[[Category: Rodriguez, L C]]
	[[Category: Schoonjans, K.]]		[[Category: Schoonjans, K]]
	[[Category: Disease mutation]]		[[Category: Disease mutation]]
	[[Category: Dna-binding]]		[[Category: Dna-binding]]

OCA at 06:22, 10 October 2014

2014-10-10T06:22:36Z

← Older revision		Revision as of 06:22, 10 October 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3cs4\| PDB=3cs4 \| SCENE= }}~~		==Structure-based design of a superagonist ligand for the vitamin D nuclear receptor==
	===Structure-based design of a superagonist ligand for the vitamin D nuclear receptor===		<StructureSection load='3cs4' size='340' side='right' caption='[[3cs4]], [[Resolution\|resolution]] 2.00Å' scene=''>
	~~{{ABSTRACT_PUBMED_18420145}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3cs4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CS4 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COV:(1S,3R,5Z,7E,14BETA,17ALPHA)-17-[(2S,4S)-4-(2-HYDROXY-2-METHYLPROPYL)-2-METHYLTETRAHYDROFURAN-2-YL]-9,10-SECOANDROSTA-5,7,10-TRIENE-1,3-DIOL'>COV</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3cs6\|3cs6]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VDR, NR1I1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3cs4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cs4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cs4 RCSB], [http://www.ebi.ac.uk/pdbsum/3cs4 PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref> <ref>PMID:8381803</ref> <ref>PMID:1652893</ref> <ref>PMID:2177843</ref> <ref>PMID:8106618</ref> <ref>PMID:8392085</ref> <ref>PMID:7828346</ref> <ref>PMID:8675579</ref> <ref>PMID:8961271</ref> <ref>PMID:9005998</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref> <ref>PMID:10678179</ref> <ref>PMID:15728261</ref> <ref>PMID:16913708</ref>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cs/3cs4_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Vitamin D nuclear receptor (VDR), a ligand-dependent transcriptional regulator, is an important target for multiple clinical applications, such as osteoporosis and cancer. Since exacerbated increase of calcium serum level is currently associated with VDR ligands action, superagonists with low calcium serum levels have been developed. Based on the crystal structures of human VDR (hVDR) bound to 1alpha,25-dihydroxyvitamin D(3) and superagonists-notably, KH1060-we designed a superagonist ligand. In order to optimize the aliphatic side chain conformation with a subsequent entropy benefit, we incorporated an oxolane ring and generated two stereo diasteromers, AMCR277A and AMCR277B. Only AMCR277A exhibits superagonist activity in vitro, but is as calcemic in vivo as the natural ligand. The crystal structures of the complexes between the ligand binding domain of hVDR and these ligands provide a rational approach to the design of more potent superagonist ligands for potential clinical application.

	~~==Disease==~~		Structure-based design of a superagonist ligand for the vitamin D nuclear receptor.,Hourai S, Rodrigues LC, Antony P, Reina-San-Martin B, Ciesielski F, Magnier BC, Schoonjans K, Mourino A, Rochel N, Moras D Chem Biol. 2008 Apr;15(4):383-92. PMID:18420145<ref>PMID:18420145</ref>
	~~[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are~~ the ~~cause of rickets~~ vitamin D-~~dependent type 2A~~ (~~VDDR2A~~) ~~[MIM~~:~~[http://omim.org/entry/277440 277440]]~~. ~~A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>~~PMID:~~2849209</ref><ref>PMID:8381803</ref><ref>PMID:1652893</ref><ref>PMID:2177843</ref><ref>PMID:8106618</ref><ref>PMID:8392085</ref><ref>PMID:7828346</ref><ref>PMID:8675579</ref><ref>PMID:8961271</ref>~~<ref>PMID:~~9005998~~</ref>

	~~==Function==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[http:~~/~~/www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action~~ of ~~vitamin D3 by controlling~~ the ~~expression of hormone sensitive genes~~. ~~Regulates transcription~~ of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<~~ref~~>~~PMID:16252006</ref><ref>PMID:10678179</ref><ref>PMID:15728261</ref><ref>PMID:16913708~~</~~ref~~>		</div>

	==~~About this Structure~~==		==See Also==
	[[~~3cs4~~]] ~~is a 1 chain structure with sequence from~~ [~~http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens~~]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA~~].		*[[Sandbox vdr\|Sandbox vdr]]
			*[[Vitamin D receptor\|Vitamin D receptor]]
	==~~Reference~~==		== References ==
	~~<ref group="xtra">PMID:018420145</ref>~~<references ~~group="xtra"~~/><~~references~~/>		<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Antony, P.]]		[[Category: Antony, P.]]

OCA at 23:48, 24 March 2013

2013-03-24T23:48:03Z

← Older revision		Revision as of 23:48, 24 March 2013
Line 1:		Line 1:
	~~[[Image:3cs4.png\|left\|200px]]~~

	{{STRUCTURE_3cs4\| PDB=3cs4 \| SCENE= }}		{{STRUCTURE_3cs4\| PDB=3cs4 \| SCENE= }}
			===Structure-based design of a superagonist ligand for the vitamin D nuclear receptor===
			{{ABSTRACT_PUBMED_18420145}}

	===~~Structure~~-~~based design~~ of ~~a superagonist ligand for the~~ vitamin D ~~nuclear receptor===~~		==Disease==
			[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Defects in VDR are the cause of rickets vitamin D-dependent type 2A (VDDR2A) [MIM:[http://omim.org/entry/277440 277440]]. A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.<ref>PMID:2849209</ref><ref>PMID:8381803</ref><ref>PMID:1652893</ref><ref>PMID:2177843</ref><ref>PMID:8106618</ref><ref>PMID:8392085</ref><ref>PMID:7828346</ref><ref>PMID:8675579</ref><ref>PMID:8961271</ref><ref>PMID:9005998</ref>

	~~{{ABSTRACT_PUBMED_18420145}}~~		==Function==
			[[http://www.uniprot.org/uniprot/VDR_HUMAN VDR_HUMAN]] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:16252006</ref><ref>PMID:10678179</ref><ref>PMID:15728261</ref><ref>PMID:16913708</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:018420145</ref><references group="xtra"/>		<ref group="xtra">PMID:018420145</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Antony, P.]]		[[Category: Antony, P.]]

OCA: Protected "3cs4" [edit=sysop:move=sysop]

2013-01-07T18:28:23Z

Protected "3cs4" [edit=sysop:move=sysop]

← Older revision	Revision as of 18:28, 7 January 2013
(No difference)

OCA at 18:28, 7 January 2013

2013-01-07T18:28:20Z

← Older revision		Revision as of 18:28, 7 January 2013
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	~~{{Seed}}~~
	[[Image:3cs4.png\|left\|200px]]		[[Image:3cs4.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3cs4", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_3cs4\| PDB=3cs4 \| SCENE= }}		{{STRUCTURE_3cs4\| PDB=3cs4 \| SCENE= }}

	===Structure-based design of a superagonist ligand for the vitamin D nuclear receptor===		===Structure-based design of a superagonist ligand for the vitamin D nuclear receptor===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_18420145}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 18420145 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_18420145}}		{{ABSTRACT_PUBMED_18420145}}

	==About this Structure==		==About this Structure==
	~~3CS4~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA].		[[3cs4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~18420145~~</ref><references group="xtra"/>		<ref group="xtra">PMID:018420145</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Antony, P.]]		[[Category: Antony, P.]]
Line 41:		Line 29:
	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	~~[[Category: Polymorphism]]~~
	[[Category: Receptor]]		[[Category: Receptor]]
	[[Category: Superagonist]]		[[Category: Superagonist]]
Line 47:		Line 34:
	[[Category: Transcription regulation]]		[[Category: Transcription regulation]]
	[[Category: Vdr]]		[[Category: Vdr]]
	~~[[Category: Zinc]]~~
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 04:53:08 2009''~~

OCA at 02:53, 17 February 2009

2009-02-17T02:53:09Z

← Older revision		Revision as of 02:53, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
	3CS4 is a ~~[[Single protein]]~~ structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA].		3CS4 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CS4 OCA].

	==Reference==		==Reference==
	Structure-based design of a superagonist ligand for the vitamin D nuclear receptor., Hourai S, Rodrigues LC, Antony P, Reina-San-Martin B, Ciesielski F, Magnier BC, Schoonjans K, Mourino A, Rochel N, Moras D, Chem Biol. 2008 Apr;15(4):383-92. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/18420145 18420145]~~		<ref group="xtra">PMID:18420145</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	~~[[Category: Single protein]]~~
	[[Category: Antony, P.]]		[[Category: Antony, P.]]
	[[Category: Ciesielski, F.]]		[[Category: Ciesielski, F.]]
Line 51:		Line 50:
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Mon Jul 28 08~~:16:~~29 2008~~''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 04:53:08 2009''