Structural highlights
FunctionFIMH_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 PubMedAntagonists of the FimH adhesin, a protein almost universally present at the extremity of type-1 fimbriae expressed by Escherichia coli, have been abundantly in the spotlight as alternative treatments of urinary tract infections. The antagonists function as bacterial antiadhesives through highly specific alpha-d-mannose binding in a charged and polar pocket at the tip of the FimH lectin domain and by the stacking of alkyl or aromatic moieties substituted on the mannose with two tyrosine residues (Tyr48 and Tyr137) at the entrance of the mannose-binding pocket. Using high-resolution crystal data, interaction energies are calculated for the different observed aromatic stacking modes between the tyrosines and the antagonist. The dispersion component of the interaction energy correlates with the observed electron density. The quantum chemical reactivity descriptors local hardness and polarizability were successfully validated as prediction tools for ligand affinity in the tyrosine gate of FimH and therefore have potential for rapid drug screening. Validation of Reactivity Descriptors to Assess the Aromatic Stacking within the Tyrosine Gate of FimH.,Roos G, Wellens A, Touaibia M, Yamakawa N, Geerlings P, Roy R, Wyns L, Bouckaert J ACS Med Chem Lett. 2013 Sep 13;4(11):1085-90. doi: 10.1021/ml400269v. eCollection, 2013 Nov 14. PMID:24900609[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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