3mcy
From Proteopedia
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| - | + | ==Crystal structure of FimH lectin domain bound to biphenyl mannoside meta-methyl ester.== | |
| - | + | <StructureSection load='3mcy' size='340' side='right' caption='[[3mcy]], [[Resolution|resolution]] 2.90Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3mcy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MCY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MCY FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZH1:METHYL+4-(ALPHA-D-MANNOPYRANOSYLOXY)BIPHENYL-3-CARBOXYLATE'>ZH1</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fimH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</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=3mcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mcy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mcy RCSB], [http://www.ebi.ac.uk/pdbsum/3mcy PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | FimH-mediated cellular adhesion to mannosylated proteins is critical in the ability of uropathogenic E. coli (UPEC) to colonize and invade the bladder epithelium during urinary tract infection. We describe the discovery and optimization of potent small-molecule FimH bacterial adhesion antagonists based on alpha-d-mannose 1-position anomeric glycosides using X-ray structure-guided drug design. Optimized biarylmannosides display low nanomolar binding affinity for FimH in a fluorescence polarization assay and submicromolar cellular activity in a hemagglutination (HA) functional cell assay of bacterial adhesion. X-ray crystallography demonstrates that the biphenyl moiety makes several key interactions with the outer surface of FimH including pi-pi interactions with Tyr-48 and an H-bonding electrostatic interaction with the Arg-98/Glu-50 salt bridge. Dimeric analogues linked through the biaryl ring show an impressive 8-fold increase in potency relative to monomeric matched pairs and represent the most potent FimH antagonists identified to date. The FimH antagonists described herein hold great potential for development as novel therapeutics for the effective treatment of urinary tract infections. | ||
| - | + | Structure-Based Drug Design and Optimization of Mannoside Bacterial FimH Antagonists.,Han Z, Pinkner JS, Ford B, Obermann R, Nolan W, Wildman SA, Hobbs D, Ellenberger T, Cusumano CK, Hultgren SJ, Janetka JW J Med Chem. 2010 May 27. PMID:20507142<ref>PMID:20507142</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
| - | [[Category: Ford, B A | + | [[Category: Ford, B A]] |
| - | [[Category: Hultgren, S J | + | [[Category: Hultgren, S J]] |
[[Category: Carbohydrate binding protein]] | [[Category: Carbohydrate binding protein]] | ||
[[Category: Immunogobulin fold]] | [[Category: Immunogobulin fold]] | ||
[[Category: Lectin]] | [[Category: Lectin]] | ||
[[Category: Mannoside]] | [[Category: Mannoside]] | ||
Revision as of 17:55, 18 December 2014
Crystal structure of FimH lectin domain bound to biphenyl mannoside meta-methyl ester.
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