3ZL2

A thiazolyl-mannoside bound to FimH, orthorhombic space group

3ZL2 の概要

• エントリーDOI: 10.2210/pdb3zl2/pdb
• 関連するPDBエントリー: 3ZL1
• 分子名称: PROTEIN FIMH, N-{5-[(1R)-1-hydroxyethyl]-1,3-thiazol-2-yl}-alpha-D-mannopyranosylamine (3 entities in total)
• 機能のキーワード: cell adhesion, type-1 fimbriae, thiazole, crohn's disease, immunoglobulin
• 由来する生物種: ESCHERICHIA COLI
• 細胞内の位置: Fimbrium: P08191
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17221.15

構造登録者

Brument, S.,Sivignon, A.,Dumych, T.I.,Moreau, N.,Roos, G.,Guerardel, Y.,Chalopin, T.,Deniaud, D.,Bilyy, R.O.,Darfeuille-Michaud, A.,Bouckaert, J.,Gouin, S.G. (登録日: 2013-01-27, 公開日: 2013-07-10, 最終更新日: 2024-10-16)

主引用文献

Brument, S.,Sivignon, A.,Dumych, T.I.,Moreau, N.,Roos, G.,Guerardel, Y.,Chalopin, T.,Deniaud, D.,Bilyy, R.O.,Darfeuille-Michaud, A.,Bouckaert, J.,Gouin, S.G.
Thiazolylaminomannosides as Potent Antiadhesives of Type 1 Piliated Escherichia Coli Isolated from Crohn'S Disease Patients.
J.Med.Chem., 56:5395-, 2013

PubMed Abstract: Adherent-invasive Escherichia coli (AIEC) have previously been shown to induce gut inflammation in patients with Crohn's disease (CD). We developed a set of mannosides to prevent AIEC attachment to the gut by blocking the FimH bacterial adhesin. The crystal structure of the FimH lectin domain in complex with a lead thiazolylaminomannoside highlighted the preferential position for pharmacomodulations. A small library of analogues showing nanomolar affinity for FimH was then developed. Notably, AIEC attachment to intestinal cells was efficiently prevented by the most active compound and at around 10000-fold and 100-fold lower concentrations than mannose and the potent FimH inhibitor heptylmannoside, respectively. An ex vivo assay performed on the colonic tissue of a transgenic mouse model of CD confirmed this antiadhesive potential. Given the key role of AIEC in the chronic intestinal inflammation of CD patients, these results suggest a potential antiadhesive treatment with the FimH inhibitors developed.

PubMed: 23795713
DOI: 10.1021/JM400723N

実験手法

X-RAY DIFFRACTION (1.251 Å)