7lqk - Revision history

OCA at 15:56, 18 October 2023

OCA — Wed, 18 Oct 2023 15:56:09 GMT

←Older revision		Revision as of 15:56, 18 October 2023
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	<StructureSection load='7lqk' size='340' side='right'caption='[[7lqk]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='7lqk' size='340' side='right'caption='[[7lqk]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lqk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Aquae Aquae~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lqk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.1Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">snf, aq_2077 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=224324 AQUAE])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7lqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lqk OCA], [https://pdbe.org/7lqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lqk RCSB], [https://www.ebi.ac.uk/pdbsum/7lqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lqk 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=7lqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lqk OCA], [https://pdbe.org/7lqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lqk RCSB], [https://www.ebi.ac.uk/pdbsum/7lqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lqk ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/O67854_AQUAE O67854_AQUAE]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 17:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7lqk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7lqk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Leucine transporter\|Leucine transporter]]
		+	*[[Symporter 3D structures\|Symporter 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Aquae~~]]	+	[[Category: Aquifex aeolicus VF5]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Aguilar, J]]	+	[[Category: Aguilar J]]
-	[[Category: Font, J]]	+	[[Category: Font J]]
-	[[Category: Galli, A]]	+	[[Category: Galli A]]
-	[[Category: Ryan, R]]	+	[[Category: Ryan R]]
-	~~[[Category: Leucine transporter]]~~	+
-	~~[[Category: Transport protein]]~~	+
-	~~[[Category: Transporter~~]]	+

OCA at 14:51, 2 June 2021

OCA — Wed, 02 Jun 2021 14:51:52 GMT

←Older revision		Revision as of 14:51, 2 June 2021
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	==Crystal structure of the R375A mutant of LeuT==		==Crystal structure of the R375A mutant of LeuT==
-	<StructureSection load='7lqk' size='340' side='right'caption='[[7lqk]]' scene=''>	+	<StructureSection load='7lqk' size='340' side='right'caption='[[7lqk]], [[Resolution\|resolution]] 2.10Å' 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=7LQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lqk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquae Aquae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQK FirstGlance]. <br>
-	</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=7lqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lqk OCA], [https://pdbe.org/7lqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lqk RCSB], [https://www.ebi.ac.uk/pdbsum/7lqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lqk 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=ALA:ALANINE'>ALA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">snf, aq_2077 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=224324 AQUAE])</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=7lqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lqk OCA], [https://pdbe.org/7lqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lqk RCSB], [https://www.ebi.ac.uk/pdbsum/7lqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lqk ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Parkinson disease (PD) is a progressive, neurodegenerative disorder affecting over 6.1 million people worldwide. Although the cause of PD remains unclear, studies of highly penetrant mutations identified in early-onset familial parkinsonism have contributed to our understanding of the molecular mechanisms underlying disease pathology. Dopamine (DA) transporter (DAT) deficiency syndrome (DTDS) is a distinct type of infantile parkinsonism-dystonia that shares key clinical features with PD, including motor deficits (progressive bradykinesia, tremor, hypomimia) and altered DA neurotransmission. Here, we define structural, functional, and behavioral consequences of a Cys substitution at R445 in human DAT (hDAT R445C), identified in a patient with DTDS. We found that this R445 substitution disrupts a phylogenetically conserved intracellular (IC) network of interactions that compromise the hDAT IC gate. This is demonstrated by both Rosetta molecular modeling and fine-grained simulations using hDAT R445C, as well as EPR analysis and X-ray crystallography of the bacterial homolog leucine transporter. Notably, the disruption of this IC network of interactions supported a channel-like intermediate of hDAT and compromised hDAT function. We demonstrate that Drosophila melanogaster expressing hDAT R445C show impaired hDAT activity, which is associated with DA dysfunction in isolated brains and with abnormal behaviors monitored at high-speed time resolution. We show that hDAT R445C Drosophila exhibit motor deficits, lack of motor coordination (i.e. flight coordination) and phenotypic heterogeneity in these behaviors that is typically associated with DTDS and PD. These behaviors are linked with altered dopaminergic signaling stemming from loss of DA neurons and decreased DA availability. We rescued flight coordination with chloroquine, a lysosomal inhibitor that enhanced DAT expression in a heterologous expression system. Together, these studies shed some light on how a DTDS-linked DAT mutation underlies DA dysfunction and, possibly, clinical phenotypes shared by DTDS and PD.
		+
		+	Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia.,Aguilar JI, Cheng MH, Font J, Schwartz AC, Ledwitch K, Duran A, Mabry SJ, Belovich AN, Zhu Y, Carter AM, Shi L, Kurian MA, Fenollar-Ferrer C, Meiler J, Ryan RM, Mchaourab HS, Bahar I, Matthies HJ, Galli A Elife. 2021 May 18;10. pii: 68039. doi: 10.7554/eLife.68039. PMID:34002696<ref>PMID:34002696</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lqk" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Aquae]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Aguilar J]]	+	[[Category: Aguilar, J]]
-	[[Category: Font J]]	+	[[Category: Font, J]]
-	[[Category: Galli A]]	+	[[Category: Galli, A]]
-	[[Category: Ryan R]]	+	[[Category: Ryan, R]]
		+	[[Category: Leucine transporter]]
		+	[[Category: Transport protein]]
		+	[[Category: Transporter]]

OCA at 10:10, 19 May 2021

OCA — Wed, 19 May 2021 10:10:49 GMT

←Older revision		Revision as of 10:10, 19 May 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7lqk ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of the R375A mutant of LeuT==
-		+	<StructureSection load='7lqk' size='340' side='right'caption='[[7lqk]]' scene=''>
-	~~Authors~~: ~~Font~~, J., ~~Aguilar~~, J., ~~Galli, A~~., ~~Ryan, R~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LQK FirstGlance]. <br>
-	~~Description: Crystal structure of the R375A mutant of LeuT~~	+	</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=7lqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lqk OCA], [https://pdbe.org/7lqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lqk RCSB], [https://www.ebi.ac.uk/pdbsum/7lqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lqk ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Aguilar, J]]	+	__TOC__
-	[[Category: ~~Galli, A~~]]	+	</StructureSection>
-	[[Category: ~~Ryan, R~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Font, J~~]]	+	[[Category: Aguilar J]]
		+	[[Category: Font J]]
		+	[[Category: Galli A]]
		+	[[Category: Ryan R]]

OCA: Protected "7lqk" [edit=sysop:move=sysop]

OCA — Wed, 24 Feb 2021 05:40:44 GMT

Protected "7lqk" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:40, 24 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lqk is ON HOLD until Paper Publication Authors: Font, J., Aguilar, J., Galli, A., Ryan, R. Description: Crystal structure of the R375A mutant of L...

OCA — Wed, 24 Feb 2021 05:40:43 GMT

New page: '''Unreleased structure''' The entry 7lqk is ON HOLD until Paper Publication Authors: Font, J., Aguilar, J., Galli, A., Ryan, R. Description: Crystal structure of the R375A mutant of L...

New page

'''Unreleased structure'''

The entry 7lqk is ON HOLD until Paper Publication

Authors: Font, J., Aguilar, J., Galli, A., Ryan, R.

Description: Crystal structure of the R375A mutant of LeuT
[[Category: Unreleased Structures]]
[[Category: Aguilar, J]]
[[Category: Galli, A]]
[[Category: Ryan, R]]
[[Category: Font, J]]