6ukj - Revision history

OCA at 06:50, 11 April 2020

OCA — Sat, 11 Apr 2020 06:50:56 GMT

←Older revision		Revision as of 06:50, 11 April 2020
Line 3:		Line 3:
	<SX load='6ukj' size='340' side='right' viewer='molstar' caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>		<SX load='6ukj' size='340' side='right' viewer='molstar' caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Plaf8 Plaf8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Plaf8 Plaf8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PFBG_01689 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=57266 PLAF8])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PFBG_01689 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=57266 PLAF8])</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=6ukj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukj OCA], [http://pdbe.org/6ukj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ukj RCSB], [http://www.ebi.ac.uk/pdbsum/6ukj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukj ProSAT]</span></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=6ukj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukj OCA], [http://pdbe.org/6ukj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ukj RCSB], [http://www.ebi.ac.uk/pdbsum/6ukj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukj ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:11, 7 March 2020

OCA — Sat, 07 Mar 2020 01:11:52 GMT

←Older revision		Revision as of 01:11, 7 March 2020
Line 1:		Line 1:

	==Single-Particle Cryo-EM Structure of Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) 7G8 Isoform==		==Single-Particle Cryo-EM Structure of Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) 7G8 Isoform==
-	<~~StructureSection~~ load='6ukj' size='340' side='right'caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>	+	<SX load='6ukj' size='340' side='right' viewer='molstar' caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Plaf8 Plaf8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Plaf8 Plaf8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>
Line 20:		Line 20:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 18:52, 11 December 2019

OCA — Wed, 11 Dec 2019 18:52:30 GMT

←Older revision		Revision as of 18:52, 11 December 2019
Line 3:		Line 3:
	<StructureSection load='6ukj' size='340' side='right'caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>		<StructureSection load='6ukj' size='340' side='right'caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Plaf8 Plaf8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PFBG_01689 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=57266 PLAF8])</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=6ukj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukj OCA], [http://pdbe.org/6ukj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ukj RCSB], [http://www.ebi.ac.uk/pdbsum/6ukj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukj ProSAT]</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=6ukj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukj OCA], [http://pdbe.org/6ukj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ukj RCSB], [http://www.ebi.ac.uk/pdbsum/6ukj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukj ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The emergence and spread of drug-resistant Plasmodium falciparum impedes global efforts to control and eliminate malaria. For decades, treatment of malaria has relied on chloroquine (CQ), a safe and affordable 4-aminoquinoline that was highly effective against intra-erythrocytic asexual blood-stage parasites, until resistance arose in Southeast Asia and South America and spread worldwide(1). Clinical resistance to the chemically related current first-line combination drug piperaquine (PPQ) has now emerged regionally, reducing its efficacy(2). Resistance to CQ and PPQ has been associated with distinct sets of point mutations in the P. falciparum CQ-resistance transporter PfCRT, a 49-kDa member of the drug/metabolite transporter superfamily that traverses the membrane of the acidic digestive vacuole of the parasite(3-9). Here we present the structure, at 3.2 A resolution, of the PfCRT isoform of CQ-resistant, PPQ-sensitive South American 7G8 parasites, using single-particle cryo-electron microscopy and antigen-binding fragment technology. Mutations that contribute to CQ and PPQ resistance localize primarily to moderately conserved sites on distinct helices that line a central negatively charged cavity, indicating that this cavity is the principal site of interaction with the positively charged CQ and PPQ. Binding and transport studies reveal that the 7G8 isoform binds both drugs with comparable affinities, and that these drugs are mutually competitive. The 7G8 isoform transports CQ in a membrane potential- and pH-dependent manner, consistent with an active efflux mechanism that drives CQ resistance(5), but does not transport PPQ. Functional studies on the newly emerging PfCRT F145I and C350R mutations, associated with decreased PPQ susceptibility in Asia and South America, respectively(6,9), reveal their ability to mediate PPQ transport in 7G8 variant proteins and to confer resistance in gene-edited parasites. Structural, functional and in silico analyses suggest that distinct mechanistic features mediate the resistance to CQ and PPQ in PfCRT variants. These data provide atomic-level insights into the molecular mechanism of this key mediator of antimalarial treatment failures.
		+
		+	Structure and drug resistance of the Plasmodium falciparum transporter PfCRT.,Kim J, Tan YZ, Wicht KJ, Erramilli SK, Dhingra SK, Okombo J, Vendome J, Hagenah LM, Giacometti SI, Warren AL, Nosol K, Roepe PD, Potter CS, Carragher B, Kossiakoff AA, Quick M, Fidock DA, Mancia F Nature. 2019 Nov 27. pii: 10.1038/s41586-019-1795-x. doi:, 10.1038/s41586-019-1795-x. PMID:31776516<ref>PMID:31776516</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6ukj" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Plaf8]]
	[[Category: Carragher, B]]		[[Category: Carragher, B]]
	[[Category: Dhingra, S K]]		[[Category: Dhingra, S K]]

OCA at 08:24, 4 December 2019

OCA — Wed, 04 Dec 2019 08:24:53 GMT

←Older revision		Revision as of 08:24, 4 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6ukj ~~is ON HOLD~~	+	==Single-Particle Cryo-EM Structure of Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) 7G8 Isoform==
-		+	<StructureSection load='6ukj' size='340' side='right'caption='[[6ukj]], [[Resolution\|resolution]] 3.30Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6ukj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UKJ FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6ukj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ukj OCA], [http://pdbe.org/6ukj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ukj RCSB], [http://www.ebi.ac.uk/pdbsum/6ukj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ukj ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Carragher, B]]
		+	[[Category: Dhingra, S K]]
		+	[[Category: Erramilli, S K]]
		+	[[Category: Fidock, D A]]
		+	[[Category: Giacometti, S I]]
		+	[[Category: Hagenah, L M]]
		+	[[Category: Kim, J]]
		+	[[Category: Kossiakoff, A A]]
		+	[[Category: Mancia, F]]
		+	[[Category: Nosol, K]]
		+	[[Category: Okombo, J]]
		+	[[Category: Potter, C S]]
		+	[[Category: Quick, M]]
		+	[[Category: Roepe, P D]]
		+	[[Category: Tan, Y Z]]
		+	[[Category: Vendome, J]]
		+	[[Category: Warren, A L]]
		+	[[Category: Wicht, K J]]
		+	[[Category: Digestive vacuole of malaria parasite]]
		+	[[Category: Drug resistance]]
		+	[[Category: Membrane protein]]
		+	[[Category: Nanodisc]]
		+	[[Category: Transporter]]

OCA at 13:50, 20 November 2019

OCA — Wed, 20 Nov 2019 13:50:58 GMT

←Older revision		Revision as of 13:50, 20 November 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ukj is ON HOLD ~~until sometime in the future~~	+	The entry 6ukj is ON HOLD

	Authors:		Authors:

OCA at 05:10, 23 October 2019

OCA — Wed, 23 Oct 2019 05:10:00 GMT

←Older revision		Revision as of 05:10, 23 October 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ukj is ON HOLD	+	The entry 6ukj is ON HOLD until sometime in the future

	Authors:		Authors:

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

OCA — Wed, 16 Oct 2019 04:35:57 GMT

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

←Older revision

Revision as of 04:35, 16 October 2019

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

OCA — Wed, 16 Oct 2019 04:35:55 GMT

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

New page

'''Unreleased structure'''

The entry 6ukj is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]