4jvd - Revision history

OCA at 08:54, 20 March 2024

OCA — Wed, 20 Mar 2024 08:54:14 GMT

←Older revision		Revision as of 08:54, 20 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4jvd]] is a 1 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=4JVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JVD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4jvd]] is a 1 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=4JVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JVD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NNQ:2-NONYLQUINOLIN-4(1H)-ONE'>NNQ</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]] 2.95Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NNQ:2-NONYLQUINOLIN-4(1H)-ONE'>NNQ</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=4jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvd OCA], [https://pdbe.org/4jvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jvd RCSB], [https://www.ebi.ac.uk/pdbsum/4jvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvd 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=4jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvd OCA], [https://pdbe.org/4jvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jvd RCSB], [https://www.ebi.ac.uk/pdbsum/4jvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/A0A0H2Z7A6_PSEAB A0A0H2Z7A6_PSEAB]		[https://www.uniprot.org/uniprot/A0A0H2Z7A6_PSEAB A0A0H2Z7A6_PSEAB]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4-hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR.
-
-	Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR).,Ilangovan A, Fletcher M, Rampioni G, Pustelny C, Rumbaugh K, Heeb S, Camara M, Truman A, Chhabra SR, Emsley J, Williams P PLoS Pathog. 2013;9(7):e1003508. doi: 10.1371/journal.ppat.1003508. Epub 2013 Jul, 25. PMID:23935486<ref>PMID:23935486</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4jvd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Transcriptional activator 3D structures\|Transcriptional activator 3D structures]]		*[[Transcriptional activator 3D structures\|Transcriptional activator 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:27, 30 November 2022

OCA — Wed, 30 Nov 2022 11:27:13 GMT

←Older revision		Revision as of 11:27, 30 November 2022
Line 1:		Line 1:

	==Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ==		==Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ==
-	<StructureSection load='4jvd' size='340' side='right' caption='[[4jvd]], [[Resolution\|resolution]] 2.95Å' scene=''>	+	<StructureSection load='4jvd' size='340' side='right'caption='[[4jvd]], [[Resolution\|resolution]] 2.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4jvd]] is a 1 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=4JVD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4JVD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4jvd]] is a 1 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=4JVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JVD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NNQ:2-NONYLQUINOLIN-4(1H)-ONE'>NNQ</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NNQ:2-NONYLQUINOLIN-4(1H)-ONE'>NNQ</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jvi\|4jvi]], [[3tk3\|3tk3]]</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=4jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvd OCA], [https://pdbe.org/4jvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jvd RCSB], [https://www.ebi.ac.uk/pdbsum/4jvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvd ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">mvfR, PA14_51340, PqsR ([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=4jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvd OCA], [~~http~~://pdbe.org/4jvd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4jvd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4jvd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvd ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A0H2Z7A6_PSEAB A0A0H2Z7A6_PSEAB]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4jvd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4jvd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Transcriptional activator 3D structures\|Transcriptional activator 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Pseab~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Emsley, J~~]]	+	[[Category: Pseudomonas aeruginosa UCBPP-PA14]]
-	[[Category: ~~Ilangovan, A~~]]	+	[[Category: Emsley J]]
-	[[Category: ~~Williams, P~~]]	+	[[Category: Ilangovan A]]
-	[[Category: ~~Dna binding]]~~	+	[[Category: Williams P]]
-	~~[[Category: Gene regulation]]~~	+
-	~~[[Category: Ligand/coinducer recognition]]~~	+
-	~~[[Category: Transcription regulator~~]]	+

OCA at 12:35, 4 August 2016

OCA — Thu, 04 Aug 2016 12:35:41 GMT

←Older revision		Revision as of 12:35, 4 August 2016
Line 1:		Line 1:
-	{{STRUCTURE_4jvd\| PDB=4jvd \| SCENE= }}
-	===Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ===
-	{{ABSTRACT_PUBMED_23935486}}

-	==~~About this Structure~~==	+	==Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ==
-	[[4jvd]] is a 1 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=4JVD OCA].	+	<StructureSection load='4jvd' size='340' side='right' caption='[[4jvd]], [[Resolution\|resolution]] 2.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4jvd]] is a 1 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=4JVD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JVD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NNQ:2-NONYLQUINOLIN-4(1H)-ONE'>NNQ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jvi\|4jvi]], [[3tk3\|3tk3]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">mvfR, PA14_51340, PqsR ([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=4jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvd OCA], [http://pdbe.org/4jvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jvd RCSB], [http://www.ebi.ac.uk/pdbsum/4jvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvd ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4-hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR.

-	~~==Reference==~~	+	Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR).,Ilangovan A, Fletcher M, Rampioni G, Pustelny C, Rumbaugh K, Heeb S, Camara M, Truman A, Chhabra SR, Emsley J, Williams P PLoS Pathog. 2013;9(7):e1003508. doi: 10.1371/journal.ppat.1003508. Epub 2013 Jul, 25. PMID:23935486<ref>PMID:23935486</ref>
-	<ref ~~group="xtra"~~>PMID:~~023935486~~</ref><~~references group~~="~~xtra~~"/><references/>	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4jvd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Pseab]]		[[Category: Pseab]]
-	[[Category: Emsley, J.]]	+	[[Category: Emsley, J]]
-	[[Category: Ilangovan, A.]]	+	[[Category: Ilangovan, A]]
-	[[Category: Williams, P.]]	+	[[Category: Williams, P]]
	[[Category: Dna binding]]		[[Category: Dna binding]]
	[[Category: Gene regulation]]		[[Category: Gene regulation]]
	[[Category: Ligand/coinducer recognition]]		[[Category: Ligand/coinducer recognition]]
	[[Category: Transcription regulator]]		[[Category: Transcription regulator]]

OCA at 04:33, 13 February 2014

OCA — Thu, 13 Feb 2014 04:33:47 GMT

←Older revision		Revision as of 04:33, 13 February 2014
Line 1:		Line 1:
	{{STRUCTURE_4jvd\| PDB=4jvd \| SCENE= }}		{{STRUCTURE_4jvd\| PDB=4jvd \| SCENE= }}
	===Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ===		===Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ===
		+	{{ABSTRACT_PUBMED_23935486}}

	==About this Structure==		==About this Structure==
-	[[4jvd]] is a 1 chain structure with sequence from [http://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=4JVD OCA].	+	[[4jvd]] is a 1 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=4JVD OCA].
-	[[Category: ~~Pseudomonas aeruginosa ucbpp-pa14~~]]	+
		+	==Reference==
		+	<ref group="xtra">PMID:023935486</ref><references group="xtra"/><references/>
		+	[[Category: Pseab]]
	[[Category: Emsley, J.]]		[[Category: Emsley, J.]]
	[[Category: Ilangovan, A.]]		[[Category: Ilangovan, A.]]

OCA at 21:03, 7 August 2013

OCA — Wed, 07 Aug 2013 21:03:00 GMT

←Older revision		Revision as of 21:03, 7 August 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4jvd\| PDB=4jvd \| SCENE= }}
		+	===Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ===

-	~~The entry~~ 4jvd is ~~ON HOLD until Paper Publication~~	+	==About this Structure==
-		+	[[4jvd]] is a 1 chain structure with sequence from [http://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=4JVD OCA].
-	~~Authors~~: ~~Ilangovan, A.,~~ Emsley, J., Williams, P.	+	[[Category: Pseudomonas aeruginosa ucbpp-pa14]]
-		+	[[Category: Emsley, J.]]
-	~~Description~~: ~~Crystal structure of PqsR~~ coinducer ~~binding domain of Pseudomonas aeruginosa with ligand NHQ~~	+	[[Category: Ilangovan, A.]]
		+	[[Category: Williams, P.]]
		+	[[Category: Dna binding]]
		+	[[Category: Gene regulation]]
		+	[[Category: Ligand/coinducer recognition]]
		+	[[Category: Transcription regulator]]

OCA at 14:56, 10 July 2013

OCA — Wed, 10 Jul 2013 14:56:59 GMT

←Older revision		Revision as of 14:56, 10 July 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4jvd is ON HOLD	+	The entry 4jvd is ON HOLD until Paper Publication

	Authors: Ilangovan, A., Emsley, J., Williams, P.		Authors: Ilangovan, A., Emsley, J., Williams, P.

	Description: Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ		Description: Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ

OCA: Protected "4jvd" [edit=sysop:move=sysop]

OCA — Thu, 04 Apr 2013 01:04:32 GMT

Protected "4jvd" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:04, 4 April 2013

OCA: New page: '''Unreleased structure''' The entry 4jvd is ON HOLD Authors: Ilangovan, A., Emsley, J., Williams, P. Description: Crystal structure of PqsR coinducer binding domain of Pseudomonas aer...

OCA — Thu, 04 Apr 2013 01:04:31 GMT

New page: '''Unreleased structure''' The entry 4jvd is ON HOLD Authors: Ilangovan, A., Emsley, J., Williams, P. Description: Crystal structure of PqsR coinducer binding domain of Pseudomonas aer...

New page

'''Unreleased structure'''

The entry 4jvd is ON HOLD

Authors: Ilangovan, A., Emsley, J., Williams, P.

Description: Crystal structure of PqsR coinducer binding domain of Pseudomonas aeruginosa with ligand NHQ