4BUQ

Crystal structure of wild type FimH lectin domain in complex with heptyl alpha-D-mannopyrannoside

4BUQ の概要

• エントリーDOI: 10.2210/pdb4buq/pdb
• 分子名称: FIMH, heptyl alpha-D-mannopyranoside (3 entities in total)
• 機能のキーワード: cell adhesion, type 1 fimbriae, urinary tract infection, variable immunoglobulin fold
• 由来する生物種: ESCHERICHIA COLI UTI89
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34390.34

構造登録者

Rabbani, S.,Bouckaert, J.,Zalewski, A.,Preston, R.,Eid, S.,Thompson, A.,Puorger, C.,Glockshuber, R.,Ernst, B. (登録日: 2013-06-23, 公開日: 2014-02-19, 最終更新日: 2024-10-16)

主引用文献

Roos, G.,Wellens, A.,Touaibia, M.,Yamakawa, N.,Geerlings, P.,Roy, R.,Wyns, L.,Bouckaert, J.
Validation of Reactivity Descriptors to Assess the Aromatic Stacking within the Tyrosine Gate of Fimh
Acs Med.Chem.Lett., 4:1085-, 2013

PubMed Abstract: Antagonists 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 α-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.

PubMed: 24900609
DOI: 10.1021/ML400269V

実験手法

X-RAY DIFFRACTION (2.199 Å)