OCA at 07:31, 22 November 2023

2023-11-22T07:31:06Z

←Older revision		Revision as of 07:31, 22 November 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8pm6 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human bile salt export pump (BSEP) in complex with inhibitor GBM in nanodiscs==
		+	<StructureSection load='8pm6' size='340' side='right'caption='[[8pm6]], [[Resolution\|resolution]] 3.22Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8pm6]] 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=8PM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PM6 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.22Å</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=GBM:5-CHLORO-N-(2-{4-[(CYCLOHEXYLCARBAMOYL)SULFAMOYL]PHENYL}ETHYL)-2-METHOXYBENZAMIDE'>GBM</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=8pm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pm6 OCA], [https://pdbe.org/8pm6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pm6 RCSB], [https://www.ebi.ac.uk/pdbsum/8pm6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pm6 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/ABCBB_HUMAN ABCBB_HUMAN] Progressive familial intrahepatic cholestasis type 2;Intrahepatic cholestasis of pregnancy;Benign recurrent intrahepatic cholestasis type 2. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ABCBB_HUMAN ABCBB_HUMAN] Catalyzes the secretion of conjugated bile salts across the canalicular membrane of hepatocytes in an ATP-dependent manner (PubMed:16332456). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456).<ref>PMID:16332456</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BSEP (ABCB11) is an ATP-binding cassette transporter that is expressed in hepatocytes and extrudes bile salts into the canaliculi of the liver. BSEP dysfunction, caused by mutations or induced by drugs, is frequently associated with severe cholestatic liver disease. We report the cryo-EM structure of glibenclamide-bound human BSEP in nanodiscs, revealing the basis of small-molecule inhibition. Glibenclamide binds the apex of a central binding pocket between the transmembrane domains, preventing BSEP from undergoing conformational changes, and thus rationalizing the reduced uptake of bile salts. We further report two high-resolution structures of BSEP trapped in distinct nucleotide-bound states by using a catalytically inactivated BSEP variant (BSEP(E1244Q)) to visualize a pre-hydrolysis state, and wild-type BSEP trapped by vanadate to visualize a post-hydrolysis state. Our studies provide structural and functional insight into the mechanism of bile salt extrusion and into small-molecule inhibition of BSEP, which may rationalize drug-induced liver toxicity.

-	~~Authors~~:	+	Structural basis of bile salt extrusion and small-molecule inhibition in human BSEP.,Liu H, Irobalieva RN, Kowal J, Ni D, Nosol K, Bang-Sorensen R, Lancien L, Stahlberg H, Stieger B, Locher KP Nat Commun. 2023 Nov 10;14(1):7296. doi: 10.1038/s41467-023-43109-1. PMID:37949847<ref>PMID:37949847</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8pm6" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Bang-Sorensen R]]
		+	[[Category: Irobalieva RN]]
		+	[[Category: Kowal J]]
		+	[[Category: Lancien L]]
		+	[[Category: Liu H]]
		+	[[Category: Locher KP]]
		+	[[Category: Ni D]]
		+	[[Category: Nosol K]]
		+	[[Category: Stahlberg H]]
		+	[[Category: Stieger B]]

OCA at 04:02, 9 August 2023

2023-08-09T04:02:22Z

←Older revision		Revision as of 04:02, 9 August 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8pm6 is ON HOLD	+	The entry 8pm6 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8pm6" [edit=sysop:move=sysop]

2023-07-05T04:19:48Z

Protected "8pm6" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:19, 5 July 2023

OCA: New page: '''Unreleased structure''' The entry 8pm6 is ON HOLD Authors: Description: Category: Unreleased Structures

2023-07-05T04:19:47Z

New page: '''Unreleased structure''' The entry 8pm6 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8pm6 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8pm6 - Revision history

OCA at 07:31, 22 November 2023

OCA at 04:02, 9 August 2023

OCA: Protected "8pm6" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8pm6 is ON HOLD Authors: Description: Category: Unreleased Structures