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6g2s

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Crystal structure of FimH in complex with a pentaflourinated biphenyl alpha D-mannoside

Structural highlights

6g2s is a 9 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	fimH, b4320, JW4283 (ECOLI)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Antimicrobial 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

↑ 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. Improvement of Aglycone pi-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists. ChemMedChem. 2019 Feb 1. doi: 10.1002/cmdc.201900051. PMID:30710416 doi:http://dx.doi.org/10.1002/cmdc.201900051

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6g2s"

@@ Line 3: / Line 3: @@
 <StructureSection load='6g2s' size='340' side='right'caption='[[6g2s]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == 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>
+<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>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Ecoli]]
 [[Category: Large Structures]]
 [[Category: Cramer, J]]

6g2s

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Current revision

Crystal structure of FimH in complex with a pentaflourinated biphenyl alpha D-mannoside

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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