7ayn

Crystal structure of the lectin domain of the FimH variant Arg98Ala, in complex with Methyl 3-chloro-4-D-mannopyranosyloxy-3-biphenylcarboxylate

spinqualitylabelsall models 7ayn, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ayn is a 4 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.42Å Ligands: EDO, SBQ 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 Bacterial resistance has become an important challenge in the treatment of urinary tract infections. The underlying resistance mechanisms can most likely be circumvented with an antiadhesive approach, antagonizing the lectin FimH located at the tip of fimbriae of uropathogenic E. coli. Here we report on a novel series of FimH antagonists based on the 1-(alpha-d-mannopyranosyl)-4-phenyl-1,2,3-triazole scaffold, designed to incorporate carboxylic acid or ester functions to interact with FimH Arg98. The most potent representative of the series, ester 11e, displayed a Kd value of 7.6 nM for the lectin domain of FimH with a general conclusion that all esters outperform carboxylates in terms of affinity. Surprisingly, all compounds from this new series exhibited improved binding affinities also for the R98A mutant, indicating another possible interaction contributing to binding. Our study on 1-(alpha-d-mannopyranosyl)-4-phenyl-1,2,3-triazole-based FimH antagonists offers proof that targeting Arg98 side chain by a "chemical common sense", i.e. by introduction of the acidic moiety to form ionic bond with Arg98 is most likely unsuitable approach to boost FimH antagonists' potency. Does targeting Arg98 of FimH lead to high affinity antagonists?,Tomasic T, Rabbani S, Jakob RP, Reisner A, Jakopin Z, Maier T, Ernst B, Anderluh M Eur J Med Chem. 2020 Dec 9;211:113093. doi: 10.1016/j.ejmech.2020.113093. PMID:33340913 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adhesin 3D structures

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