6ev0 - Revision history

OCA at 07:48, 23 May 2018

OCA — Wed, 23 May 2018 07:48:59 GMT

←Older revision		Revision as of 07:48, 23 May 2018
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	<StructureSection load='6ev0' size='340' side='right' caption='[[6ev0]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='6ev0' size='340' side='right' caption='[[6ev0]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6ev0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EV0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EV0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6ev0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lismo Lismo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EV0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EV0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BYK:[(3~{R})-3-carboxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridin-8-yl]-dimethyl-azanium'>BYK</scene>, <scene name='pdbligand=C8N:[(3~{S})-3-carboxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridin-8-yl]-dimethyl-azanium'>C8N</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BYK:[(3~{R})-3-carboxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridin-8-yl]-dimethyl-azanium'>BYK</scene>, <scene name='pdbligand=C8N:[(3~{S})-3-carboxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridin-8-yl]-dimethyl-azanium'>C8N</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5f1r\|5f1r]], [[6eut\|6eut]], [[6euu\|6euu]], [[6euz\|6euz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5f1r\|5f1r]], [[6eut\|6eut]], [[6euu\|6euu]], [[6euz\|6euz]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">prfA, lmo0200 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=169963 LISMO])</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=6ev0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ev0 OCA], [http://pdbe.org/6ev0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ev0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ev0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ev0 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=6ev0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ev0 OCA], [http://pdbe.org/6ev0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ev0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ev0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ev0 ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Lismo]]
	[[Category: Almqvist, F]]		[[Category: Almqvist, F]]
	[[Category: Begum, A]]		[[Category: Begum, A]]

OCA at 08:14, 2 May 2018

OCA — Wed, 02 May 2018 08:14:41 GMT

←Older revision		Revision as of 08:14, 2 May 2018
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-	'''Unreleased structure'''

-	The ~~entry~~ 6ev0 is ~~ON HOLD until Paper~~ Publication	+	==The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (AC129)==
		+	<StructureSection load='6ev0' size='340' side='right' caption='[[6ev0]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6ev0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EV0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EV0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BYK:[(3~{R})-3-carboxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridin-8-yl]-dimethyl-azanium'>BYK</scene>, <scene name='pdbligand=C8N:[(3~{S})-3-carboxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridin-8-yl]-dimethyl-azanium'>C8N</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5f1r\|5f1r]], [[6eut\|6eut]], [[6euu\|6euu]], [[6euz\|6euz]]</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=6ev0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ev0 OCA], [http://pdbe.org/6ev0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ev0 RCSB], [http://www.ebi.ac.uk/pdbsum/6ev0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ev0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PRFA_LISMO PRFA_LISMO]] Positively regulates expression of listeriolysin, of 1-phosphadidylinositol phosphodiesterase (PI-PLC) and other virulence factors.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure-guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intraprotein "tunnel" as the main inhibitor binding site (AI), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix-turn-helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-AI selective PrfA inhibitors with potent antivirulence properties.

-	~~Authors: Begum~~, A., ~~Hall~~, M., ~~Grundstrom~~, C~~., Cairns~~, A~~.G.~~, ~~Kulen~~, M., ~~Lindgren, M.~~, Johansson, J., Almqvist, F.~~, Sauer, U~~.H.~~, Sauer-Eriksson, A~~.E.	+	Structure-Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of Listeria monocytogenes.,Kulen M, Lindgren M, Hansen S, Cairns AG, Grundstrom C, Begum A, van der Lingen I, Brannstrom K, Hall M, Sauer UH, Johansson J, Sauer-Eriksson AE, Almqvist F J Med Chem. 2018 Apr 27. doi: 10.1021/acs.jmedchem.8b00289. PMID:29667825<ref>PMID:29667825</ref>

-	~~Description: The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with~~ a ~~ring~~-~~fused 2~~-~~pyridone (AC129)~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Johansson~~, J]]	+	<div class="pdbe-citations 6ev0" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Cairns~~, A.G]]	+	== References ==
-	[[Category: ~~Sauer-Eriksson~~, A.E]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Almqvist, F]]
		+	[[Category: Begum, A]]
		+	[[Category: Cairns, A G]]
	[[Category: Grundstrom, C]]		[[Category: Grundstrom, C]]
	[[Category: Hall, M]]		[[Category: Hall, M]]
-	[[Category: ~~Sauer~~, ~~U.H]]~~	+	[[Category: Johansson, J]]
-	~~[[Category: Begum, A]]~~	+
-	~~[[Category: Lindgren, M~~]]	+
	[[Category: Kulen, M]]		[[Category: Kulen, M]]
-	[[Category: ~~Almqvist~~, F]]	+	[[Category: Lindgren, M]]
		+	[[Category: Sauer, U H]]
		+	[[Category: Sauer-Eriksson, A E]]
		+	[[Category: 2-pyridone]]
		+	[[Category: Dna binding]]
		+	[[Category: Dna binding protein]]
		+	[[Category: Drug design]]
		+	[[Category: Listeria monocytogene]]
		+	[[Category: Transcription regulator]]

OCA at 06:09, 6 December 2017

OCA — Wed, 06 Dec 2017 06:09:45 GMT

←Older revision		Revision as of 06:09, 6 December 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6ev0 is ON HOLD	+	The entry 6ev0 is ON HOLD until Paper Publication

	Authors: Begum, A., Hall, M., Grundstrom, C., Cairns, A.G., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E.		Authors: Begum, A., Hall, M., Grundstrom, C., Cairns, A.G., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E.
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	[[Category: Sauer-Eriksson, A.E]]		[[Category: Sauer-Eriksson, A.E]]
	[[Category: Grundstrom, C]]		[[Category: Grundstrom, C]]
-	[[Category: Begum, A]]
-	[[Category: Almqvist, F]]
	[[Category: Hall, M]]		[[Category: Hall, M]]
	[[Category: Sauer, U.H]]		[[Category: Sauer, U.H]]
		+	[[Category: Begum, A]]
	[[Category: Lindgren, M]]		[[Category: Lindgren, M]]
	[[Category: Kulen, M]]		[[Category: Kulen, M]]
		+	[[Category: Almqvist, F]]

OCA at 05:11, 29 November 2017

OCA — Wed, 29 Nov 2017 05:11:32 GMT

←Older revision		Revision as of 05:11, 29 November 2017
Line 3:		Line 3:
	The entry 6ev0 is ON HOLD		The entry 6ev0 is ON HOLD

-	Authors: Begum, A., Hall, M., Grundstrom, C., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E.	+	Authors: Begum, A., Hall, M., Grundstrom, C., Cairns, A.G., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E.

-	Description: The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (~~compound 11~~)	+	Description: The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (AC129)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Johansson, J]]		[[Category: Johansson, J]]
		+	[[Category: Cairns, A.G]]
	[[Category: Sauer-Eriksson, A.E]]		[[Category: Sauer-Eriksson, A.E]]
	[[Category: Grundstrom, C]]		[[Category: Grundstrom, C]]

OCA: Protected "6ev0" [edit=sysop:move=sysop]

OCA — Wed, 08 Nov 2017 06:43:59 GMT

Protected "6ev0" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:43, 8 November 2017

OCA: New page: '''Unreleased structure''' The entry 6ev0 is ON HOLD Authors: Begum, A., Hall, M., Grundstrom, C., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E...

OCA — Wed, 08 Nov 2017 06:43:58 GMT

New page: '''Unreleased structure''' The entry 6ev0 is ON HOLD Authors: Begum, A., Hall, M., Grundstrom, C., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E...

New page

'''Unreleased structure'''

The entry 6ev0 is ON HOLD

Authors: Begum, A., Hall, M., Grundstrom, C., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E.

Description: The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (compound 11)
[[Category: Unreleased Structures]]
[[Category: Johansson, J]]
[[Category: Sauer-Eriksson, A.E]]
[[Category: Grundstrom, C]]
[[Category: Begum, A]]
[[Category: Almqvist, F]]
[[Category: Hall, M]]
[[Category: Sauer, U.H]]
[[Category: Lindgren, M]]
[[Category: Kulen, M]]