6g2s: Difference between revisions
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<StructureSection load='6g2s' size='340' side='right'caption='[[6g2s]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='6g2s' size='340' side='right'caption='[[6g2s]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6g2s]] is a 9 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G2S FirstGlance]. <br> | <table><tr><td colspan='2'>[[6g2s]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G2S FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EJN:(2~{R},3~{S},4~{S},5~{S},6~{R})-2-(hydroxymethyl)-6-[4-[2,3,4,5,6-pentakis(fluoranyl)phenyl]phenoxy]oxane-3,4,5-triol'>EJN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EJN:(2~{R},3~{S},4~{S},5~{S},6~{R})-2-(hydroxymethyl)-6-[4-[2,3,4,5,6-pentakis(fluoranyl)phenyl]phenoxy]oxane-3,4,5-triol'>EJN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fimH, b4320, JW4283 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=6g2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g2s OCA], [http://pdbe.org/6g2s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g2s RCSB], [http://www.ebi.ac.uk/pdbsum/6g2s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g2s ProSAT]</span></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=6g2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g2s OCA], [http://pdbe.org/6g2s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g2s RCSB], [http://www.ebi.ac.uk/pdbsum/6g2s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g2s ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Ecoli]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cramer, J]] | [[Category: Cramer, J]] | ||
Latest revision as of 09:48, 17 April 2019
Crystal structure of FimH in complex with a pentaflourinated biphenyl alpha D-mannosideCrystal structure of FimH in complex with a pentaflourinated biphenyl alpha D-mannoside
Structural highlights
Function[FIMH_ECOLI] Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed. Publication Abstract from PubMedAntimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl alpha-d-mannosides leads to compounds with perfect pi-pi stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar KD values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as (1) H,(15) N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability. Improvement of Aglycone pi-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists.,Schonemann W, Cramer J, Muhlethaler T, Fiege B, Silbermann M, Rabbani S, Datwyler P, Zihlmann P, Jakob RP, Sager CP, Smiesko M, Schwardt O, Maier T, Ernst B ChemMedChem. 2019 Feb 1. doi: 10.1002/cmdc.201900051. PMID:30710416[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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