6map - Revision history

OCA at 12:52, 6 November 2024

2024-11-06T12:52:09Z

← Older revision		Revision as of 12:52, 6 November 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/YDEQ_ECOLI YDEQ_ECOLI]		[https://www.uniprot.org/uniprot/YDEQ_ECOLI YDEQ_ECOLI]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1 by replacing the carboxylate with a sulfonamide as in 50. Other groups which can accept H-bonds were also tolerated. We pursued further modifications to the biphenyl aglycone resulting in significantly improved activity. Two of the most potent compounds, 86 (IC(50) = 0.051 muM) and 90 (IC(50) = 0.034 muM), exhibited excellent metabolic stability in mouse plasma and liver microsomes but showed only limited oral bioavailability (<1%) in rats. Compound 84 also showed a good pharmacokinetic (PK) profile in mice after IP dosing with compound exposure above the IC(50) for 6 h. These new FmlH antagonists represent new antivirulence drugs for UTIs.

			Biphenyl Gal and GalNAc FmlH Lectin Antagonists of Uropathogenic E. coli (UPEC): Optimization through Iterative Rational Drug Design.,Maddirala AR, Klein R, Pinkner JS, Kalas V, Hultgren SJ, Janetka JW J Med Chem. 2019 Jan 24;62(2):467-479. doi: 10.1021/acs.jmedchem.8b01561. Epub , 2019 Jan 2. PMID:30540910<ref>PMID:30540910</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 6map" style="background-color:#fffaf0;"></div>

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

OCA at 06:27, 11 October 2023

2023-10-11T06:27:37Z

← Older revision		Revision as of 06:27, 11 October 2023
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	<StructureSection load='6map' size='340' side='right'caption='[[6map]], [[Resolution\|resolution]] 1.08Å' scene=''>		<StructureSection load='6map' size='340' side='right'caption='[[6map]], [[Resolution\|resolution]] 1.08Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6map]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Ecout Ecout~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MAP FirstGlance]. <br>		<table><tr><td colspan='2'>[[6map]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_UTI89 Escherichia coli UTI89]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MAP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JC4:2-(beta-D-galactopyranosyloxy)-5-nitro[1,1-biphenyl]-3-carboxylic+acid'>JC4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.08Å</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">b1502, fmlD, ydeQ, AC789_1c16310, ACN002_1542, B1K96_25685, BK292_08390, BN17_21261, C7B02_22960, CR538_13120, CWS33_06125, CXB56_15680, HW43_11455, RX35_00290 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=364106 ECOUT])</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JC4:2-(beta-D-galactopyranosyloxy)-5-nitro[1,1-biphenyl]-3-carboxylic+acid'>JC4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6map OCA], [~~http~~://pdbe.org/6map PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6map RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6map PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6map 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=6map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6map OCA], [https://pdbe.org/6map PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6map RCSB], [https://www.ebi.ac.uk/pdbsum/6map PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6map ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/YDEQ_ECOLI YDEQ_ECOLI]

			==See Also==
			*[[Adhesin 3D structures\|Adhesin 3D structures]]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Ecout~~]]		[[Category: Escherichia coli UTI89]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Hultgren~~, S J~~]]		[[Category: Hultgren SJ]]
	[[Category: Klein~~, R D]]~~		[[Category: Klein RD]]
	~~[[Category: Adhesin]]~~
	~~[[Category: Galactose]]~~
	~~[[Category: Lectin]]~~
	~~[[Category: Pilus]]~~
	~~[[Category: Sugar binding protein]]~~
	~~[[Category: Sugar binding protein-inhibitor complex~~]]

OCA at 10:50, 18 December 2019

2019-12-18T10:50:51Z

← Older revision		Revision as of 10:50, 18 December 2019
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	~~'''Unreleased structure'''~~

	~~The entry~~ 6map is ~~ON HOLD until Paper Publication~~		==F9 Pilus Adhesin FmlH Lectin Domain from E. coli UTI89 in Complex with Galactoside 5-nitro-2'-{[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-[1,1'-biphenyl]-3-carboxylic acid==
			<StructureSection load='6map' size='340' side='right'caption='[[6map]], [[Resolution\|resolution]] 1.08Å' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>[[6map]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecout Ecout]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MAP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MAP FirstGlance]. <br>
	~~Description~~:		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JC4:2-(beta-D-galactopyranosyloxy)-5-nitro[1,1-biphenyl]-3-carboxylic+acid'>JC4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">b1502, fmlD, ydeQ, AC789_1c16310, ACN002_1542, B1K96_25685, BK292_08390, BN17_21261, C7B02_22960, CR538_13120, CWS33_06125, CXB56_15680, HW43_11455, RX35_00290 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=364106 ECOUT])</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=6map FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6map OCA], [http://pdbe.org/6map PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6map RCSB], [http://www.ebi.ac.uk/pdbsum/6map PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6map ProSAT]</span></td></tr>
			</table>
			__TOC__
			</StructureSection>
			[[Category: Ecout]]
			[[Category: Large Structures]]
			[[Category: Hultgren, S J]]
			[[Category: Klein, R D]]
			[[Category: Adhesin]]
			[[Category: Galactose]]
			[[Category: Lectin]]
			[[Category: Pilus]]
			[[Category: Sugar binding protein]]
			[[Category: Sugar binding protein-inhibitor complex]]

OCA at 18:22, 19 September 2018

2018-09-19T18:22:52Z

← Older revision		Revision as of 18:22, 19 September 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 6map is ON HOLD		The entry 6map is ON HOLD until Paper Publication

	Authors:		Authors:

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

2018-09-05T08:53:36Z

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

← Older revision	Revision as of 08:53, 5 September 2018
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6map is ON HOLD Authors: Description: Category: Unreleased Structures

2018-09-05T08:53:34Z

New page: '''Unreleased structure''' The entry 6map is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6map is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]