7okc - Revision history

OCA at 12:51, 1 February 2024

2024-02-01T12:51:38Z

←Older revision		Revision as of 12:51, 1 February 2024
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	<StructureSection load='7okc' size='340' side='right'caption='[[7okc]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='7okc' size='340' side='right'caption='[[7okc]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7okc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7okc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=VFE:2-[2-(2-chlorophenyl)sulfanylethanoyl-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]amino]-N-methyl-ethanamide'>VFE</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]] 1.84Å</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.129 2.3.1.129] </span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=VFE:2-[2-(2-chlorophenyl)sulfanylethanoyl-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]amino]-N-methyl-ethanamide'>VFE</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=7okc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okc OCA], [https://pdbe.org/7okc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okc RCSB], [https://www.ebi.ac.uk/pdbsum/7okc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okc 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=7okc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okc OCA], [https://pdbe.org/7okc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okc RCSB], [https://www.ebi.ac.uk/pdbsum/7okc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/C3TPH2_ECOLX C3TPH2_ECOLX]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.[HAMAP-Rule:MF_00387]	+	[https://www.uniprot.org/uniprot/C3TPH2_ECOLX C3TPH2_ECOLX] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.[HAMAP-Rule:MF_00387]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Escherichia coli]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andersen~~, O A~~]]	+	[[Category: Andersen OA]]
-	[[Category: Barker, J]]	+	[[Category: Barker J]]
-	[[Category: DeJonge~~, B L.M~~]]	+	[[Category: DeJonge BLM]]
-	[[Category: Parkes~~, A L~~]]	+	[[Category: Parkes AL]]
-	[[Category: Ryan~~, M D~~]]	+	[[Category: Ryan MD]]
-	[[Category: Southey, M]]	+	[[Category: Southey M]]
-	[[Category: Zahn, M]]	+	[[Category: Zahn M]]
-	~~[[Category: Acyltransferase]]~~	+
-	~~[[Category: Fatty acid]]~~	+
-	~~[[Category: Left-handed parallel beta-helix]]~~	+
-	~~[[Category: Lipid some]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:57, 13 October 2021

2021-10-13T12:57:07Z

←Older revision		Revision as of 12:57, 13 October 2021
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	==Crystal structure of Escherichia coli LpxA in complex with compound 1==		==Crystal structure of Escherichia coli LpxA in complex with compound 1==
-	<StructureSection load='7okc' size='340' side='right'caption='[[7okc]]' scene=''>	+	<StructureSection load='7okc' size='340' side='right'caption='[[7okc]], [[Resolution\|resolution]] 1.84Å' 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=7OKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7okc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKC 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=7okc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okc OCA], [https://pdbe.org/7okc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okc RCSB], [https://www.ebi.ac.uk/pdbsum/7okc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okc 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=VFE:2-[2-(2-chlorophenyl)sulfanylethanoyl-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]amino]-N-methyl-ethanamide'>VFE</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine_O-acyltransferase Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.129 2.3.1.129] </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=7okc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okc OCA], [https://pdbe.org/7okc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okc RCSB], [https://www.ebi.ac.uk/pdbsum/7okc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/C3TPH2_ECOLX C3TPH2_ECOLX]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.[HAMAP-Rule:MF_00387]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	This study describes a novel series of UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of Pseudomonas aeruginosa LpxA with no activity against Escherichia coli LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against P. aeruginosa LpxA (best half-maximal inhibitory concentration (IC50) <5 nM) and cellular activity against P. aeruginosa (best minimal inhibitory concentration (MIC) of 4 mug/mL). Lack of activity against E. coli was maintained (IC50 > 20 muM and MIC > 128 mug/mL). The mode of action of analogues was confirmed through genetic analyses. As expected, compounds were active against multidrug-resistant isolates. Further optimization of pharmacokinetics is needed before efficacy studies in mouse infection models can be attempted. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa.
		+
		+	Discovery of Novel UDP-N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa.,Ryan MD, Parkes AL, Corbett D, Dickie AP, Southey M, Andersen OA, Stein DB, Barbeau OR, Sanzone A, Thommes P, Barker J, Cain R, Compper C, Dejob M, Dorali A, Etheridge D, Evans S, Faulkner A, Gadouleau E, Gorman T, Haase D, Holbrow-Wilshaw M, Krulle T, Li X, Lumley C, Mertins B, Napier S, Odedra R, Papadopoulos K, Roumpelakis V, Spear K, Trimby E, Williams J, Zahn M, Keefe AD, Zhang Y, Soutter HT, Centrella PA, Clark MA, Cuozzo JW, Dumelin CE, Deng B, Hunt A, Sigel EA, Troast DM, DeJonge BLM J Med Chem. 2021 Sep 27. doi: 10.1021/acs.jmedchem.1c00888. PMID:34569791<ref>PMID:34569791</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7okc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andersen OA]]	+	[[Category: Andersen, O A]]
-	[[Category: Barker J]]	+	[[Category: Barker, J]]
-	[[Category: DeJonge ~~BLM~~]]	+	[[Category: DeJonge, B L.M]]
-	[[Category: Parkes AL]]	+	[[Category: Parkes, A L]]
-	[[Category: Ryan MD]]	+	[[Category: Ryan, M D]]
-	[[Category: Southey M]]	+	[[Category: Southey, M]]
-	[[Category: Zahn M]]	+	[[Category: Zahn, M]]
		+	[[Category: Acyltransferase]]
		+	[[Category: Fatty acid]]
		+	[[Category: Left-handed parallel beta-helix]]
		+	[[Category: Lipid some]]
		+	[[Category: Transferase]]

OCA at 05:32, 6 October 2021

2021-10-06T05:32:44Z

←Older revision		Revision as of 05:32, 6 October 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7okc ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of Escherichia coli LpxA in complex with compound 1==
-		+	<StructureSection load='7okc' size='340' side='right'caption='[[7okc]]' scene=''>
-	~~Authors~~: ~~Ryan, M~~.D.~~, Parkes, A~~.L.~~, Southey, M~~., ~~Andersen, O~~.A., ~~Zahn, M~~., ~~Barker, J~~., ~~DeJonge, B~~.L.M.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKC FirstGlance]. <br>
-	~~Description: Crystal structure of Escherichia coli LpxA in complex with compound 1~~	+	</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=7okc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7okc OCA], [https://pdbe.org/7okc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7okc RCSB], [https://www.ebi.ac.uk/pdbsum/7okc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7okc ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Dejonge, B.L.M~~]]	+	__TOC__
-	[[Category: ~~Ryan, M.D~~]]	+	</StructureSection>
-	[[Category: ~~Southey, M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Zahn, M~~]]	+	[[Category: Andersen OA]]
-	[[Category: ~~Andersen, O.A~~]]	+	[[Category: Barker J]]
-	[[Category: ~~Barker, J~~]]	+	[[Category: DeJonge BLM]]
-	[[Category: ~~Parkes, A.L~~]]	+	[[Category: Parkes AL]]
		+	[[Category: Ryan MD]]
		+	[[Category: Southey M]]
		+	[[Category: Zahn M]]

OCA at 13:36, 2 June 2021

2021-06-02T13:36:50Z

←Older revision		Revision as of 13:36, 2 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7okc is ON HOLD	+	The entry 7okc is ON HOLD until Paper Publication

	Authors: Ryan, M.D., Parkes, A.L., Southey, M., Andersen, O.A., Zahn, M., Barker, J., DeJonge, B.L.M.		Authors: Ryan, M.D., Parkes, A.L., Southey, M., Andersen, O.A., Zahn, M., Barker, J., DeJonge, B.L.M.
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	Description: Crystal structure of Escherichia coli LpxA in complex with compound 1		Description: Crystal structure of Escherichia coli LpxA in complex with compound 1
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Andersen, O.A]]
-	[[Category: Barker, J]]
-	[[Category: Parkes, A.L]]
	[[Category: Dejonge, B.L.M]]		[[Category: Dejonge, B.L.M]]
	[[Category: Ryan, M.D]]		[[Category: Ryan, M.D]]
	[[Category: Southey, M]]		[[Category: Southey, M]]
	[[Category: Zahn, M]]		[[Category: Zahn, M]]
		+	[[Category: Andersen, O.A]]
		+	[[Category: Barker, J]]
		+	[[Category: Parkes, A.L]]

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

2021-05-26T08:09:27Z

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

←Older revision

Revision as of 08:09, 26 May 2021

OCA: New page: '''Unreleased structure''' The entry 7okc is ON HOLD Authors: Ryan, M.D., Parkes, A.L., Southey, M., Andersen, O.A., Zahn, M., Barker, J., DeJonge, B.L.M. Description: Crystal structur...

2021-05-26T08:09:26Z

New page: '''Unreleased structure''' The entry 7okc is ON HOLD Authors: Ryan, M.D., Parkes, A.L., Southey, M., Andersen, O.A., Zahn, M., Barker, J., DeJonge, B.L.M. Description: Crystal structur...

New page

'''Unreleased structure'''

The entry 7okc is ON HOLD

Authors: Ryan, M.D., Parkes, A.L., Southey, M., Andersen, O.A., Zahn, M., Barker, J., DeJonge, B.L.M.

Description: Crystal structure of Escherichia coli LpxA in complex with compound 1
[[Category: Unreleased Structures]]
[[Category: Andersen, O.A]]
[[Category: Barker, J]]
[[Category: Parkes, A.L]]
[[Category: Dejonge, B.L.M]]
[[Category: Ryan, M.D]]
[[Category: Southey, M]]
[[Category: Zahn, M]]