5awj - Revision history

OCA at 09:06, 20 March 2024

OCA — Wed, 20 Mar 2024 09:06:03 GMT

←Older revision		Revision as of 09:06, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [https://pdbe.org/5awj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [https://www.ebi.ac.uk/pdbsum/5awj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5awj 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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [https://pdbe.org/5awj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [https://www.ebi.ac.uk/pdbsum/5awj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5awj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/VDR_RAT VDR_RAT] 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:17227670</ref>		[https://www.uniprot.org/uniprot/VDR_RAT VDR_RAT] 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:17227670</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	1alpha,25-Dihydroxyvitamin D3 exerts its actions by binding to vitamin D receptor (VDR). We are continuing the study related to the alteration of pocket structure of VDR by 22-alkyl substituent of ligands and the relationships between the alteration and agonistic/antagonistic activity. Previously we reported that compounds 2 (22-H), 3 (22S-Et), and 4 (22S-Bu) are VDR agonist, partial agonist and antagonist, respectively. Here, we describe the synthesis and biological evaluation of 22S-hexyl analog 5 (22S-Hex), which was designed to be a stronger VDR antagonist than 4. Unexpectedly, 5 showed partial agonistic but not antagonistic activity when bound to VDR, indicating that it is not necessarily true that the bulkier the side chain is, the stronger the antagonistic activity will be. X-ray crystallographic analysis of the VDR-ligand-binding domain (VDR-LBD) accommodating compound 5 indicated that the partial agonist activity of 5 is dependent on the mixed population of the agonistic and antagonistic conformations. Binding of compound 5 may not bring the complex into the only antagonistic conformation due to the large conformational change of the VDR-LBD. From this study it was found that fine tuning of agonistic/antagonistic activity for VDR is possible by 22-alkyl chain length of ligands.
-
-	Fine tuning of agonistic/antagonistic activity for vitamin D receptor by 22-alkyl chain length of ligands: 22S-Hexyl compound unexpectedly restored agonistic activity.,Anami Y, Sakamaki Y, Itoh T, Inaba Y, Nakabayashi M, Ikura T, Ito N, Yamamoto K Bioorg Med Chem. 2015 Nov 15;23(22):7274-81. doi: 10.1016/j.bmc.2015.10.026. Epub, 2015 Oct 26. PMID:26515040<ref>PMID:26515040</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5awj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 06:28, 31 May 2023

OCA — Wed, 31 May 2023 06:28:15 GMT

←Older revision		Revision as of 06:28, 31 May 2023
Line 3:		Line 3:
	<StructureSection load='5awj' size='340' side='right'caption='[[5awj]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='5awj' size='340' side='right'caption='[[5awj]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5awk\|5awk]]</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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [https://pdbe.org/5awj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [https://www.ebi.ac.uk/pdbsum/5awj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5awj ProSAT]</span></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=10116 Buffalo rat])~~</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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [~~http~~://pdbe.org/5awj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5awj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5awj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/VDR_RAT VDR_RAT]] 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:17227670</ref> [[http://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref>	+	[https://www.uniprot.org/uniprot/VDR_RAT VDR_RAT] 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:17227670</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[Vitamin D receptor\|Vitamin D receptor]]	+	*[[Vitamin D receptor 3D structures\|Vitamin D receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Buffalo rat~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Anami, Y]]	+	[[Category: Rattus norvegicus]]
-	[[Category: Ikura, T]]	+	[[Category: Anami Y]]
-	[[Category: Inaba, Y]]	+	[[Category: Ikura T]]
-	[[Category: Ito, N]]	+	[[Category: Inaba Y]]
-	[[Category: Itoh, T]]	+	[[Category: Ito N]]
-	[[Category: Nakabayashi, M]]	+	[[Category: Itoh T]]
-	[[Category: Yamamoto, K]]	+	[[Category: Nakabayashi M]]
-	~~[[Category: Co-factor]]~~	+	[[Category: Yamamoto K]]
-	~~[[Category: Rxr]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Vdre]]~~	+
-	~~[[Category: Vitamin d3~~]]	+

OCA at 07:31, 3 July 2019

OCA — Wed, 03 Jul 2019 07:31:00 GMT

←Older revision		Revision as of 07:31, 3 July 2019
Line 1:		Line 1:
		+
	==Crystal structure of VDR-LBD/partial agonist complex: 22S-hexyl analogue==		==Crystal structure of VDR-LBD/partial agonist complex: 22S-hexyl analogue==
-	<StructureSection load='5awj' size='340' side='right' caption='[[5awj]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='5awj' size='340' side='right'caption='[[5awj]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5awk\|5awk]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5awk\|5awk]]</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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [http://pdbe.org/5awj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [http://www.ebi.ac.uk/pdbsum/5awj PDBsum]</span></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=10116 Buffalo rat])</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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [http://pdbe.org/5awj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [http://www.ebi.ac.uk/pdbsum/5awj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5awj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5awj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5awj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Vitamin D receptor\|Vitamin D receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
		+	[[Category: Large Structures]]
	[[Category: Anami, Y]]		[[Category: Anami, Y]]
	[[Category: Ikura, T]]		[[Category: Ikura, T]]

OCA at 18:58, 1 December 2015

OCA — Tue, 01 Dec 2015 18:58:35 GMT

←Older revision		Revision as of 18:58, 1 December 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of VDR-LBD/partial agonist complex: 22S-hexyl analogue==
		+	<StructureSection load='5awj' size='340' side='right' caption='[[5awj]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5awj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AWJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AWJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=YSL:(1R,3R)-5-[(2E)-2-[(1R,3AS,7AR)-1-[(2R,3S)-3-(2-HYDROXYETHYL)NONAN-2-YL]-7A-METHYL-2,3,3A,5,6,7-HEXAHYDRO-1H-INDEN-4-YLIDENE]ETHYLIDENE]-2-METHYLIDENE-CYCLOHEXANE-1,3-DIOL'>YSL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5awk\|5awk]]</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=5awj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5awj OCA], [http://pdbe.org/5awj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5awj RCSB], [http://www.ebi.ac.uk/pdbsum/5awj PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/VDR_RAT VDR_RAT]] 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:17227670</ref> [[http://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	1alpha,25-Dihydroxyvitamin D3 exerts its actions by binding to vitamin D receptor (VDR). We are continuing the study related to the alteration of pocket structure of VDR by 22-alkyl substituent of ligands and the relationships between the alteration and agonistic/antagonistic activity. Previously we reported that compounds 2 (22-H), 3 (22S-Et), and 4 (22S-Bu) are VDR agonist, partial agonist and antagonist, respectively. Here, we describe the synthesis and biological evaluation of 22S-hexyl analog 5 (22S-Hex), which was designed to be a stronger VDR antagonist than 4. Unexpectedly, 5 showed partial agonistic but not antagonistic activity when bound to VDR, indicating that it is not necessarily true that the bulkier the side chain is, the stronger the antagonistic activity will be. X-ray crystallographic analysis of the VDR-ligand-binding domain (VDR-LBD) accommodating compound 5 indicated that the partial agonist activity of 5 is dependent on the mixed population of the agonistic and antagonistic conformations. Binding of compound 5 may not bring the complex into the only antagonistic conformation due to the large conformational change of the VDR-LBD. From this study it was found that fine tuning of agonistic/antagonistic activity for VDR is possible by 22-alkyl chain length of ligands.

-	~~The entry 5awj is ON HOLD until Paper Publication~~	+	Fine tuning of agonistic/antagonistic activity for vitamin D receptor by 22-alkyl chain length of ligands: 22S-Hexyl compound unexpectedly restored agonistic activity.,Anami Y, Sakamaki Y, Itoh T, Inaba Y, Nakabayashi M, Ikura T, Ito N, Yamamoto K Bioorg Med Chem. 2015 Nov 15;23(22):7274-81. doi: 10.1016/j.bmc.2015.10.026. Epub, 2015 Oct 26. PMID:26515040<ref>PMID:26515040</ref>

-	~~Authors: Anami~~, Y.~~, Itoh, T~~.~~, Inaba, Y., Nakabayashi, M., Ikura, T., Ito, N., Yamamoto, K~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of VDR-LBD~~/~~partial agonist complex: 22S-hexyl analogue~~	+	<div class="pdbe-citations 5awj" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
-	[[Category: ~~Nakabayashi~~, M]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Anami, Y]]
		+	[[Category: Ikura, T]]
	[[Category: Inaba, Y]]		[[Category: Inaba, Y]]
-	[[Category: Yamamoto, K]]
-	[[Category: Anami, Y]]
	[[Category: Ito, N]]		[[Category: Ito, N]]
	[[Category: Itoh, T]]		[[Category: Itoh, T]]
-	[[Category: ~~Ikura~~, T]]	+	[[Category: Nakabayashi, M]]
		+	[[Category: Yamamoto, K]]
		+	[[Category: Co-factor]]
		+	[[Category: Rxr]]
		+	[[Category: Transcription]]
		+	[[Category: Vdre]]
		+	[[Category: Vitamin d3]]

OCA at 09:57, 2 September 2015

OCA — Wed, 02 Sep 2015 09:57:40 GMT

←Older revision		Revision as of 09:57, 2 September 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Anami, Y., Itoh, T., Inaba, Y., Nakabayashi, M., Ikura, T., Ito, N., Yamamoto, K.		Authors: Anami, Y., Itoh, T., Inaba, Y., Nakabayashi, M., Ikura, T., Ito, N., Yamamoto, K.

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

OCA — Wed, 15 Jul 2015 11:43:24 GMT

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

←Older revision

Revision as of 11:43, 15 July 2015

OCA: New page: '''Unreleased structure''' The entry 5awj is ON HOLD Authors: Anami, Y., Itoh, T., Inaba, Y., Nakabayashi, M., Ikura, T., Ito, N., Yamamoto, K. Description: Crystal structure of VDR-LB...

OCA — Wed, 15 Jul 2015 11:43:23 GMT

New page: '''Unreleased structure''' The entry 5awj is ON HOLD Authors: Anami, Y., Itoh, T., Inaba, Y., Nakabayashi, M., Ikura, T., Ito, N., Yamamoto, K. Description: Crystal structure of VDR-LB...

New page

'''Unreleased structure'''

The entry 5awj is ON HOLD

Authors: Anami, Y., Itoh, T., Inaba, Y., Nakabayashi, M., Ikura, T., Ito, N., Yamamoto, K.

Description: Crystal structure of VDR-LBD/partial agonist complex: 22S-hexyl analogue
[[Category: Unreleased Structures]]
[[Category: Nakabayashi, M]]
[[Category: Inaba, Y]]
[[Category: Yamamoto, K]]
[[Category: Anami, Y]]
[[Category: Ito, N]]
[[Category: Itoh, T]]
[[Category: Ikura, T]]