OCA at 06:52, 9 December 2020

OCA — Wed, 09 Dec 2020 06:52:28 GMT

←Older revision		Revision as of 06:52, 9 December 2020
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	==Human TRPC5 in complex with Pico145 (HC-608)==		==Human TRPC5 in complex with Pico145 (HC-608)==
-	<StructureSection load='6ysn' size='340' side='right'caption='[[6ysn]]' scene=''>	+	<StructureSection load='6ysn' size='340' side='right'caption='[[6ysn]], [[Resolution\|resolution]] 3.00Å' 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=6YSN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YSN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ysn]] is a 4 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=6YSN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YSN 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=6ysn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ysn OCA], [http://pdbe.org/6ysn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ysn RCSB], [http://www.ebi.ac.uk/pdbsum/6ysn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ysn 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=PJQ:7-[(4-chlorophenyl)methyl]-3-methyl-1-(3-oxidanylpropyl)-8-[3-(trifluoromethyloxy)phenoxy]purine-2,6-dione'>PJQ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TRPC5, TRP5 ([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=6ysn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ysn OCA], [http://pdbe.org/6ysn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ysn RCSB], [http://www.ebi.ac.uk/pdbsum/6ysn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ysn ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	TRPC1/4/5 channels are non-specific cation channels implicated in a wide variety of diseases, and TRPC1/4/5 inhibitors have recently entered clinical trials. However, fundamental and translational studies require a better understanding of TRPC1/4/5 channel regulation by endogenous and exogenous factors. Although several potent and selective TRPC1/4/5 modulators have been reported, the paucity of mechanistic insights into their modes-of-action remains a barrier to the development of new chemical probes and drug candidates. Xanthine-based modulators include the most potent and selective TRPC1/4/5 inhibitors described to date, as well as TRPC5 activators. Our previous studies suggest that xanthines interact with a, so far, elusive pocket of TRPC1/4/5 channels that is essential to channel gating. Here we report the structure of a small-molecule-bound TRPC1/4/5 channel-human TRPC5 in complex with the xanthine Pico145-to 3.0 A. We found that Pico145 binds to a conserved lipid binding site of TRPC5, where it displaces a bound phospholipid. Our findings explain the mode-of-action of xanthine-based TRPC1/4/5 modulators, and suggest a structural basis for TRPC1/4/5 modulation by endogenous factors such as (phospho)lipids and Zn(2+) ions. These studies lay the foundations for the structure-based design of new generations of TRPC1/4/5 modulators.
		+
		+	Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site.,Wright DJ, Simmons KJ, Johnson RM, Beech DJ, Muench SP, Bon RS Commun Biol. 2020 Nov 23;3(1):704. doi: 10.1038/s42003-020-01437-8. PMID:33230284<ref>PMID:33230284</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6ysn" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bon RS]]	+	[[Category: Bon, R S]]
-	[[Category: Johnson RM]]	+	[[Category: Johnson, R M]]
-	[[Category: Muench SP]]	+	[[Category: Muench, S P]]
-	[[Category: Wright DJ]]	+	[[Category: Wright, D J]]
		+	[[Category: Inhibitor]]
		+	[[Category: Ion channel]]
		+	[[Category: Membrane protein]]
		+	[[Category: Small molecule]]
		+	[[Category: Tetramer]]

OCA at 07:48, 2 December 2020

OCA — Wed, 02 Dec 2020 07:48:10 GMT

←Older revision		Revision as of 07:48, 2 December 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6ysn is ~~ON HOLD until Paper Publication~~	+	==Human TRPC5 in complex with Pico145 (HC-608)==
-		+	<StructureSection load='6ysn' size='340' side='right'caption='[[6ysn]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YSN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YSN 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=6ysn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ysn OCA], [http://pdbe.org/6ysn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ysn RCSB], [http://www.ebi.ac.uk/pdbsum/6ysn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ysn ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bon RS]]
		+	[[Category: Johnson RM]]
		+	[[Category: Muench SP]]
		+	[[Category: Wright DJ]]

OCA at 08:09, 12 August 2020

OCA — Wed, 12 Aug 2020 08:09:34 GMT

←Older revision		Revision as of 08:09, 12 August 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 29 Apr 2020 05:30:03 GMT

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

←Older revision

Revision as of 05:30, 29 April 2020

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

OCA — Wed, 29 Apr 2020 05:30:01 GMT

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

New page

'''Unreleased structure'''

The entry 6ysn is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6ysn - Revision history

OCA at 06:52, 9 December 2020

OCA at 07:48, 2 December 2020

OCA at 08:09, 12 August 2020

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

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