7oka - Revision history

OCA at 12:51, 1 February 2024

OCA — Thu, 01 Feb 2024 12:51:34 GMT

←Older revision		Revision as of 12:51, 1 February 2024
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	<StructureSection load='7oka' size='340' side='right'caption='[[7oka]], [[Resolution\|resolution]] 2.74Å' scene=''>		<StructureSection load='7oka' size='340' side='right'caption='[[7oka]], [[Resolution\|resolution]] 2.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7oka]] is a 30 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7oka]] is a 30 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PA7 Pseudomonas aeruginosa PA7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VFT:2-(2-chlorophenyl)sulfanyl-~{N}-[(4-cyanophenyl)methyl]-~{N}-(1~{H}-imidazol-4-ylmethyl)ethanamide'>VFT</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]] 2.74Å</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VFT:2-(2-chlorophenyl)sulfanyl-~{N}-[(4-cyanophenyl)methyl]-~{N}-(1~{H}-imidazol-4-ylmethyl)ethanamide'>VFT</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=7oka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oka OCA], [https://pdbe.org/7oka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oka RCSB], [https://www.ebi.ac.uk/pdbsum/7oka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oka 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=7oka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oka OCA], [https://pdbe.org/7oka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oka RCSB], [https://www.ebi.ac.uk/pdbsum/7oka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oka ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/~~LPXA_PSEA7 LPXA_PSEA7]~~] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.	+	[https://www.uniprot.org/uniprot/LPXA_PSEAE LPXA_PSEAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7oka" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7oka" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[UDP-N-acetylglucosamine acyltransferase\|UDP-N-acetylglucosamine acyltransferase]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Andersen~~, O A~~]]	+	[[Category: Pseudomonas aeruginosa PA7]]
-	[[Category: Barker, J]]	+	[[Category: Andersen OA]]
-	[[Category: DeJonge~~, B L.M~~]]	+	[[Category: Barker J]]
-	[[Category: Parkes~~, A L~~]]	+	[[Category: DeJonge BLM]]
-	[[Category: Ryan~~, M D~~]]	+	[[Category: Parkes AL]]
-	[[Category: Southey, M]]	+	[[Category: Ryan MD]]
-	[[Category: Zahn, M]]	+	[[Category: Southey M]]
-	~~[[Category: Acyltransferase]]~~	+	[[Category: Zahn M]]
-	~~[[Category: Fatty acid]]~~	+
-	~~[[Category: Left-handed parallel beta-helix]]~~	+
-	~~[[Category: Lipid some]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 15:53, 27 October 2021

OCA — Wed, 27 Oct 2021 15:53:51 GMT

←Older revision		Revision as of 15:53, 27 October 2021
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	==Crystal structure of Pseudomonas aeruginosa LpxA in complex with compound 14==		==Crystal structure of Pseudomonas aeruginosa LpxA in complex with compound 14==
-	<StructureSection load='7oka' size='340' side='right'caption='[[7oka]]' scene=''>	+	<StructureSection load='7oka' size='340' side='right'caption='[[7oka]], [[Resolution\|resolution]] 2.74Å' 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=7OKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7oka]] is a 30 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKA 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=7oka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oka OCA], [https://pdbe.org/7oka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oka RCSB], [https://www.ebi.ac.uk/pdbsum/7oka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oka 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VFT:2-(2-chlorophenyl)sulfanyl-~{N}-[(4-cyanophenyl)methyl]-~{N}-(1~{H}-imidazol-4-ylmethyl)ethanamide'>VFT</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=7oka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oka OCA], [https://pdbe.org/7oka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oka RCSB], [https://www.ebi.ac.uk/pdbsum/7oka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oka ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/LPXA_PSEA7 LPXA_PSEA7]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.
		+	<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 7oka" 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 11:44, 13 October 2021

OCA — Wed, 13 Oct 2021 11:44:45 GMT

←Older revision		Revision as of 11:44, 13 October 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7oka ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of Pseudomonas aeruginosa LpxA in complex with compound 14==
-		+	<StructureSection load='7oka' size='340' side='right'caption='[[7oka]]' 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=7OKA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OKA FirstGlance]. <br>
-	~~Description: Crystal structure of Pseudomonas aeruginosa LpxA in complex with compound 14~~	+	</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=7oka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oka OCA], [https://pdbe.org/7oka PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oka RCSB], [https://www.ebi.ac.uk/pdbsum/7oka PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oka 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

OCA — Wed, 02 Jun 2021 13:36:46 GMT

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

-	The entry 7oka is ON HOLD	+	The entry 7oka 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 Pseudomonas aeruginosa LpxA in complex with compound 14		Description: Crystal structure of Pseudomonas aeruginosa LpxA in complex with compound 14
	[[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 "7oka" [edit=sysop:move=sysop]

OCA — Wed, 26 May 2021 08:09:22 GMT

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

←Older revision

Revision as of 08:09, 26 May 2021

OCA: New page: '''Unreleased structure''' The entry 7oka 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...

OCA — Wed, 26 May 2021 08:09:21 GMT

New page: '''Unreleased structure''' The entry 7oka 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 7oka 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 Pseudomonas aeruginosa LpxA in complex with compound 14
[[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]]