6maq

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(New page: '''Unreleased structure''' The entry 6maq is ON HOLD Authors: Klein, R.D., Hultgren, S.J. Description: F9 Pilus Adhesin FmlH Lectin Domain from E. coli UTI89 in Complex with Galactosid...)
Current revision (12:52, 6 November 2024) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 6maq is ON HOLD
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==F9 Pilus Adhesin FmlH Lectin Domain from E. coli UTI89 in Complex with Galactoside 2'-{[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-nitro-[1,1'-biphenyl]-3-carboxylic acid==
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<StructureSection load='6maq' size='340' side='right'caption='[[6maq]], [[Resolution|resolution]] 1.31&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6maq]] 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=6MAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MAQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.31&#8491;</td></tr>
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<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=JCD:3-[2-[(2~{S},3~{R},4~{R},5~{R},6~{R})-3-acetamido-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-2-yl]oxyphenyl]-5-nitro-benzoic+acid'>JCD</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6maq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6maq OCA], [https://pdbe.org/6maq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6maq RCSB], [https://www.ebi.ac.uk/pdbsum/6maq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6maq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/YDEQ_ECOLI YDEQ_ECOLI]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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 (&lt;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.
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Authors: Klein, R.D., Hultgren, S.J.
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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>
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Description: F9 Pilus Adhesin FmlH Lectin Domain from E. coli UTI89 in Complex with Galactoside 2'-{[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-nitro-[1,1'-biphenyl]-3-carboxylic acid
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Klein, R.D]]
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<div class="pdbe-citations 6maq" style="background-color:#fffaf0;"></div>
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[[Category: Hultgren, S.J]]
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==See Also==
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*[[Adhesin 3D structures|Adhesin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Escherichia coli UTI89]]
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[[Category: Large Structures]]
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[[Category: Hultgren SJ]]
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[[Category: Klein RD]]

Current revision

F9 Pilus Adhesin FmlH Lectin Domain from E. coli UTI89 in Complex with Galactoside 2'-{[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-nitro-[1,1'-biphenyl]-3-carboxylic acid

PDB ID 6maq

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