6maq: Difference between revisions
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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... |
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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== | |||
<StructureSection load='6maq' size='340' side='right'caption='[[6maq]], [[Resolution|resolution]] 1.31Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.31Å</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=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> | |||
<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> | |||
</table> | |||
== Function == | |||
[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> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6maq" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Adhesin 3D structures|Adhesin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli UTI89]] | |||
[[Category: Large Structures]] | |||
[[Category: Hultgren SJ]] | |||
[[Category: Klein RD]] | |||
Latest revision as of 12:52, 6 November 2024
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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