6v9s - Revision history

OCA at 08:06, 11 October 2023

OCA — Wed, 11 Oct 2023 08:06:59 GMT

←Older revision		Revision as of 08:06, 11 October 2023
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	<StructureSection load='6v9s' size='340' side='right'caption='[[6v9s]], [[Resolution\|resolution]] 3.50Å' scene=''>		<StructureSection load='6v9s' size='340' side='right'caption='[[6v9s]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6v9s]] 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=6V9S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6V9S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6v9s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pyrococcus_abyssi_GE5 Pyrococcus abyssi GE5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V9S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=JHC:[(2S)-2-[(2S)-butan-2-yl]-4-(5-chloro-1,3-benzoxazol-2-yl)-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone'>JHC</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</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]] 3.5Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCRTR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=JHC:[(2S)-2-[(2S)-butan-2-yl]-4-(5-chloro-1,3-benzoxazol-2-yl)-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone'>JHC</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6v9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9s OCA], [~~http~~://pdbe.org/6v9s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6v9s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6v9s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9s 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=6v9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9s OCA], [https://pdbe.org/6v9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v9s RCSB], [https://www.ebi.ac.uk/pdbsum/6v9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/OX1R_HUMAN OX1R_HUMAN]] Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. Seems to be exclusively coupled to the G(q) subclass of heteromeric G proteins, which activates the phospholipase C mediated signaling cascade (By similarity).	+	[https://www.uniprot.org/uniprot/OX1R_HUMAN OX1R_HUMAN] Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. Seems to be exclusively coupled to the G(q) subclass of heteromeric G proteins, which activates the phospholipase C mediated signaling cascade (By similarity).[https://www.uniprot.org/uniprot/Q9V2J8_PYRAB Q9V2J8_PYRAB]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6v9s" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6v9s" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Orexin and Orexin receptor\|Orexin and Orexin receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Drabek, M]]	+	[[Category: Pyrococcus abyssi GE5]]
-	[[Category: Gmeiner, P]]	+	[[Category: Drabek M]]
-	[[Category: Hellmann, J]]	+	[[Category: Gmeiner P]]
-	[[Category: Huebner, H]]	+	[[Category: Hellmann J]]
-	[[Category: Kolb, P]]	+	[[Category: Huebner H]]
-	[[Category: Kraus, F]]	+	[[Category: Kolb P]]
-	[[Category: Proell, T]]	+	[[Category: Kraus F]]
-	[[Category: Rosenbaum~~, D M~~]]	+	[[Category: Proell T]]
-	[[Category: Weikert, D]]	+	[[Category: Rosenbaum DM]]
-	[[Category: Yin, J]]	+	[[Category: Weikert D]]
-	~~[[Category: Gpcr]]~~	+	[[Category: Yin J]]
-	~~[[Category: Orexin receptor]]~~	+
-	~~[[Category: Selective ligand]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 10:03, 12 August 2020

OCA — Wed, 12 Aug 2020 10:03:17 GMT

←Older revision		Revision as of 10:03, 12 August 2020
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	==Structure-based development of subtype-selective orexin 1 receptor antagonists==		==Structure-based development of subtype-selective orexin 1 receptor antagonists==
-	<StructureSection load='6v9s' size='340' side='right'caption='[[6v9s]]' scene=''>	+	<StructureSection load='6v9s' size='340' side='right'caption='[[6v9s]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V9S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V9S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6v9s]] 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=6V9S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V9S FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9s OCA], [http://pdbe.org/6v9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v9s RCSB], [http://www.ebi.ac.uk/pdbsum/6v9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9s ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=JHC:[(2S)-2-[(2S)-butan-2-yl]-4-(5-chloro-1,3-benzoxazol-2-yl)-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone'>JHC</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCRTR1 ([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://proteopedia.org/fgij/fg.htm?mol=6v9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9s OCA], [http://pdbe.org/6v9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v9s RCSB], [http://www.ebi.ac.uk/pdbsum/6v9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9s ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/OX1R_HUMAN OX1R_HUMAN]] Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. Seems to be exclusively coupled to the G(q) subclass of heteromeric G proteins, which activates the phospholipase C mediated signaling cascade (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Orexins are neuropeptides that activate the rhodopsin-like G protein-coupled receptors OX1R and OX2R. The orexin system plays an important role in the regulation of the sleep-wake cycle and the regulation of feeding and emotions. The nonselective orexin receptor antagonist suvorexant has been the first drug on the market targeting the orexin system and is prescribed for the treatment of insomnia. Subtype-selective OX1R antagonists are valuable tools to further investigate the functions and physiological role of the OX1R in vivo and promising lead compounds for the treatment of drug addiction, anxiety, pain or obesity. Starting from the OX1R and OX2R crystal structures bound to suvorexant, we exploited a single amino acid difference in the orthosteric binding site by using molecular docking and structure-based drug design to optimize ligand interactions with the OX1R while introducing repulsive interactions with the OX2R. A newly established enantiospecific synthesis provided ligands showing up to 75-fold selectivity for the OX1R over the OX2R subtype. The structure of a new OX1R antagonist with subnanomolar affinity (JH112) was determined by crystallography in complex with the OX1R and corresponded closely to the docking-predicted geometry. JH112 exhibits high selectivity over a panel of different GPCRs, is able to cross the blood-brain barrier and acts as slowly diffusing and insurmountable antagonist for Gq protein activation and in particular beta-arrestin-2 recruitment at OX1R. This study demonstrates the potential of structure-based drug design to develop more subtype-selective GPCR ligands with potentially reduced side effects and provides an attractive probe molecule and lead compound.
		+
		+	Structure-based development of a subtype-selective orexin 1 receptor antagonist.,Hellmann J, Drabek M, Yin J, Gunera J, Proll T, Kraus F, Langmead CJ, Hubner H, Weikert D, Kolb P, Rosenbaum DM, Gmeiner P Proc Natl Acad Sci U S A. 2020 Jul 15. pii: 2002704117. doi:, 10.1073/pnas.2002704117. PMID:32669442<ref>PMID:32669442</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6v9s" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Drabek M]]	+	[[Category: Drabek, M]]
-	[[Category: Gmeiner P]]	+	[[Category: Gmeiner, P]]
-	[[Category: Hellmann J]]	+	[[Category: Hellmann, J]]
-	[[Category: Huebner H]]	+	[[Category: Huebner, H]]
-	[[Category: Kolb P]]	+	[[Category: Kolb, P]]
-	[[Category: Kraus F]]	+	[[Category: Kraus, F]]
-	[[Category: Proell T]]	+	[[Category: Proell, T]]
-	[[Category: Rosenbaum DM]]	+	[[Category: Rosenbaum, D M]]
-	[[Category: Weikert D]]	+	[[Category: Weikert, D]]
-	[[Category: Yin J]]	+	[[Category: Yin, J]]
		+	[[Category: Gpcr]]
		+	[[Category: Orexin receptor]]
		+	[[Category: Selective ligand]]
		+	[[Category: Signaling protein]]

OCA at 11:36, 29 July 2020

OCA — Wed, 29 Jul 2020 11:36:49 GMT

←Older revision		Revision as of 11:36, 29 July 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6v9s is ~~ON HOLD until Paper Publication~~	+	==Structure-based development of subtype-selective orexin 1 receptor antagonists==
-		+	<StructureSection load='6v9s' size='340' side='right'caption='[[6v9s]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V9S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V9S FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v9s OCA], [http://pdbe.org/6v9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v9s RCSB], [http://www.ebi.ac.uk/pdbsum/6v9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v9s ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Drabek M]]
		+	[[Category: Gmeiner P]]
		+	[[Category: Hellmann J]]
		+	[[Category: Huebner H]]
		+	[[Category: Kolb P]]
		+	[[Category: Kraus F]]
		+	[[Category: Proell T]]
		+	[[Category: Rosenbaum DM]]
		+	[[Category: Weikert D]]
		+	[[Category: Yin J]]

OCA at 08:06, 26 February 2020

OCA — Wed, 26 Feb 2020 08:06:01 GMT

←Older revision		Revision as of 08:06, 26 February 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6v9s is ON HOLD	+	The entry 6v9s is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6v9s" [edit=sysop:move=sysop]

OCA — Wed, 25 Dec 2019 07:33:09 GMT

Protected "6v9s" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:33, 25 December 2019

OCA: New page: '''Unreleased structure''' The entry 6v9s is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 25 Dec 2019 07:33:08 GMT

New page: '''Unreleased structure''' The entry 6v9s is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6v9s is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]