6maw
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[6maw]] 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=6MAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MAW FirstGlance]. <br> | <table><tr><td colspan='2'>[[6maw]] 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=6MAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MAW 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]] 1.75Å</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]] 1.75Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JC7:N-[2 | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JC7:~{N}-[(2~{S},3~{R},4~{R},5~{R},6~{R})-6-(hydroxymethyl)-2-[2-[3-(methylsulfonylamino)phenyl]-3-(trifluoromethyl)phenoxy]-4,5-bis(oxidanyl)oxan-3-yl]ethanamide'>JC7</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=6maw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6maw OCA], [https://pdbe.org/6maw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6maw RCSB], [https://www.ebi.ac.uk/pdbsum/6maw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6maw 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=6maw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6maw OCA], [https://pdbe.org/6maw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6maw RCSB], [https://www.ebi.ac.uk/pdbsum/6maw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6maw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== 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 6maw" 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> | ||
Current revision
F9 Pilus Adhesin FmlH Lectin Domain from E. coli UTI89 in Complex with Galactoside N-[(2S,3R,4R,5R,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-{[S-methyl-6-(trifluoromethyl)-[1,1'-biphenyl]-3'-yl]oxy}oxan-3-yl]acetamide
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