6mww - Revision history

OCA at 14:45, 13 March 2024

OCA — Wed, 13 Mar 2024 14:45:38 GMT

←Older revision		Revision as of 14:45, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6mww' size='340' side='right'caption='[[6mww]], [[Resolution\|resolution]] 2.76Å' scene=''>		<StructureSection load='6mww' size='340' side='right'caption='[[6mww]], [[Resolution\|resolution]] 2.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mww]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Pseab Pseab~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MWW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mww]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_UCBPP-PA14 Pseudomonas aeruginosa UCBPP-PA14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MWW FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=K5J:4~~-[~~3-(methylsulfonyl)phenoxy~~]~~-N-[(1R,3R,5R)-~~2~~-oxobicyclo[3~~.~~1.0]hexan-3-yl]butanamide'>K5J</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]] 2.76Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~lasR, PA14_45960~~ ([~~http://www~~.~~ncbi~~.~~nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208963 PSEAB~~])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K5J:4-[3-(methylsulfonyl)phenoxy]-N-[(1R,3R,5R)-2-oxobicyclo[3.1.0]hexan-3-yl]butanamide'>K5J</scene></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=6mww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mww OCA], [~~http~~://pdbe.org/6mww PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mww RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mww PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mww 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=6mww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mww OCA], [https://pdbe.org/6mww PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mww RCSB], [https://www.ebi.ac.uk/pdbsum/6mww PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mww ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/LASR_PSEAE LASR_PSEAE] Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.
-	~~Bacteria use a cell-cell communication process called quorum sensing to coordinate collective behaviors~~. ~~Quorum sensing relies on production and group-wide detection of extracellular signal molecules called autoinducers~~. ~~Here, we probe the activity~~ of ~~the Pseudomonas aeruginosa LasR quorum-sensing receptor using synthetic agonists based on the structure of the native homoserine lactone autoinducer~~. ~~The synthetic compounds range from low~~ to ~~high potency, and agonist activity tracks with~~ the ability of the agonist to stabilize the LasR protein. Structural analyses of the LasR ligand binding domain complexed with representative synthetic agonists reveal two modes of ligand binding, one mimicking the canonical autoinducer binding arrangement, and the other with the lactone head group rotated approximately 150 degrees . Iterative mutagenesis combined with chemical synthesis reveals the amino acid residues and the chemical moieties, respectively, that are key to enabling each mode of binding. Simultaneous alteration of LasR residues Thr75, Tyr93, and Ala127 converts low-potency compounds into high-potency compounds and converts ligands that are nearly inactive into low-potency compounds. These results show that the LasR binding pocket displays significant flexibility in accommodating different ligands. The ability of LasR to bind ligands in different conformations, and in so doing, alter their potency as agonists, could explain the difficulties that have been encountered in the development of competitive LasR inhibitors.	+

-	An Autoinducer Analogue Reveals an Alternative Mode of Ligand Binding for the LasR Quorum-Sensing Receptor.,Paczkowski JE, McCready AR, Cong JP, Li Z, Jeffrey PD, Smith CD, Henke BR, Hughson FM, Bassler BL ACS Chem Biol. 2019 Mar 15;14(3):378-389. doi: 10.1021/acschembio.8b00971. Epub, 2019 Mar 4. PMID:30763066<ref>PMID:30763066</ref>	+	==See Also==
-		+	*[[Transcriptional activator 3D structures\|Transcriptional activator 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6mww" style="background-color:#fffaf0;"></div>~~	+
-	== ~~References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Pseab~~]]	+	[[Category: Pseudomonas aeruginosa UCBPP-PA14]]
-	[[Category: Bassler~~, B L~~]]	+	[[Category: Bassler BL]]
-	[[Category: Paczkowski~~, J E]]~~	+	[[Category: Paczkowski JE]]
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcriptional activator~~]]	+

OCA at 06:11, 10 October 2019

OCA — Thu, 10 Oct 2019 06:11:37 GMT

←Older revision		Revision as of 06:11, 10 October 2019
Line 3:		Line 3:
	<StructureSection load='6mww' size='340' side='right'caption='[[6mww]], [[Resolution\|resolution]] 2.76Å' scene=''>		<StructureSection load='6mww' size='340' side='right'caption='[[6mww]], [[Resolution\|resolution]] 2.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mww]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MWW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mww]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseab Pseab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MWW FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K5J:4-[3-(methylsulfonyl)phenoxy]-N-[(1R,3R,5R)-2-oxobicyclo[3.1.0]hexan-3-yl]butanamide'>K5J</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K5J:4-[3-(methylsulfonyl)phenoxy]-N-[(1R,3R,5R)-2-oxobicyclo[3.1.0]hexan-3-yl]butanamide'>K5J</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">lasR, PA14_45960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208963 PSEAB])</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=6mww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mww OCA], [http://pdbe.org/6mww PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mww RCSB], [http://www.ebi.ac.uk/pdbsum/6mww PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mww 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=6mww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mww OCA], [http://pdbe.org/6mww PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mww RCSB], [http://www.ebi.ac.uk/pdbsum/6mww PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mww ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Bacteria use a cell-cell communication process called quorum sensing to coordinate collective behaviors. Quorum sensing relies on production and group-wide detection of extracellular signal molecules called autoinducers. Here, we probe the activity of the Pseudomonas aeruginosa LasR quorum-sensing receptor using synthetic agonists based on the structure of the native homoserine lactone autoinducer. The synthetic compounds range from low to high potency, and agonist activity tracks with the ability of the agonist to stabilize the LasR protein. Structural analyses of the LasR ligand binding domain complexed with representative synthetic agonists reveal two modes of ligand binding, one mimicking the canonical autoinducer binding arrangement, and the other with the lactone head group rotated approximately 150 degrees . Iterative mutagenesis combined with chemical synthesis reveals the amino acid residues and the chemical moieties, respectively, that are key to enabling each mode of binding. Simultaneous alteration of LasR residues Thr75, Tyr93, and Ala127 converts low-potency compounds into high-potency compounds and converts ligands that are nearly inactive into low-potency compounds. These results show that the LasR binding pocket displays significant flexibility in accommodating different ligands. The ability of LasR to bind ligands in different conformations, and in so doing, alter their potency as agonists, could explain the difficulties that have been encountered in the development of competitive LasR inhibitors.
		+
		+	An Autoinducer Analogue Reveals an Alternative Mode of Ligand Binding for the LasR Quorum-Sensing Receptor.,Paczkowski JE, McCready AR, Cong JP, Li Z, Jeffrey PD, Smith CD, Henke BR, Hughson FM, Bassler BL ACS Chem Biol. 2019 Mar 15;14(3):378-389. doi: 10.1021/acschembio.8b00971. Epub, 2019 Mar 4. PMID:30763066<ref>PMID:30763066</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6mww" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Pseab]]
	[[Category: Bassler, B L]]		[[Category: Bassler, B L]]
	[[Category: Paczkowski, J E]]		[[Category: Paczkowski, J E]]
	[[Category: Transcription]]		[[Category: Transcription]]
	[[Category: Transcriptional activator]]		[[Category: Transcriptional activator]]

OCA at 07:07, 3 April 2019

OCA — Wed, 03 Apr 2019 07:07:52 GMT

←Older revision		Revision as of 07:07, 3 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6mww is ~~ON HOLD until Paper Publication~~	+	==LasR LBD:BB0126 complex==
-		+	<StructureSection load='6mww' size='340' side='right'caption='[[6mww]], [[Resolution\|resolution]] 2.76Å' scene=''>
-	~~Authors~~: ~~Bassler~~, B.L., ~~Paczkowski~~, J.E.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6mww]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MWW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MWW FirstGlance]. <br>
-	~~Description~~: ~~LasR LBD~~:~~BB0126 complex~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K5J:4-[3-(methylsulfonyl)phenoxy]-N-[(1R,3R,5R)-2-oxobicyclo[3.1.0]hexan-3-yl]butanamide'>K5J</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=6mww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mww OCA], [http://pdbe.org/6mww PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mww RCSB], [http://www.ebi.ac.uk/pdbsum/6mww PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mww ProSAT]</span></td></tr>
-	[[Category: Bassler, B.L]]	+	</table>
-	[[Category: Paczkowski, J.E]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bassler, B L]]
		+	[[Category: Paczkowski, J E]]
		+	[[Category: Transcription]]
		+	[[Category: Transcriptional activator]]

OCA at 19:02, 2 December 2018

OCA — Sun, 02 Dec 2018 19:02:49 GMT

←Older revision		Revision as of 19:02, 2 December 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Bassler, B.L., Paczkowski, J.E.		Authors: Bassler, B.L., Paczkowski, J.E.

-	Description: LasR LBD:~~mBTL~~ complex	+	Description: LasR LBD:BB0126 complex
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Bassler, B.L]]		[[Category: Bassler, B.L]]
	[[Category: Paczkowski, J.E]]		[[Category: Paczkowski, J.E]]

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

OCA — Wed, 07 Nov 2018 10:54:35 GMT

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

←Older revision

Revision as of 10:54, 7 November 2018

OCA: New page: '''Unreleased structure''' The entry 6mww is ON HOLD Authors: Bassler, B.L., Paczkowski, J.E. Description: LasR LBD:mBTL complex Category: Unreleased Structures [[Category: Bassler...

OCA — Wed, 07 Nov 2018 10:54:34 GMT

New page: '''Unreleased structure''' The entry 6mww is ON HOLD Authors: Bassler, B.L., Paczkowski, J.E. Description: LasR LBD:mBTL complex Category: Unreleased Structures [[Category: Bassler...

New page

'''Unreleased structure'''

The entry 6mww is ON HOLD

Authors: Bassler, B.L., Paczkowski, J.E.

Description: LasR LBD:mBTL complex
[[Category: Unreleased Structures]]
[[Category: Bassler, B.L]]
[[Category: Paczkowski, J.E]]