5D2A

Bifunctional dendrimers

5D2A の概要

• エントリーDOI: 10.2210/pdb5d2a/pdb
• 分子名称: Fucose-binding lectin, ZDC-ALA-PRO-ALA-LYS-PHE-CYS-ALA-PRO-ALA-PHB-GAL, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: lectinb, pseudomonas, dendrimer, biofilm, bifunctional, sugar binding protein
• 由来する生物種: Pseudomonas aeruginosa; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 25511.74

構造登録者

Michaud, G.,Visini, R.,Stocker, A.,Darbre, T.,Reymond, J.L. (登録日: 2015-08-05, 公開日: 2016-02-10, 最終更新日: 2024-11-20)

主引用文献

Michaud, G.,Visini, R.,Bergmann, M.,Salerno, G.,Bosco, R.,Gillon, E.,Richichi, B.,Nativi, C.,Imberty, A.,Stocker, A.,Darbre, T.,Reymond, J.L.
Overcoming antibiotic resistance inPseudomonas aeruginosabiofilms using glycopeptide dendrimers.
Chem Sci, 7:166-182, 2016

PubMed Abstract: Antibiotic resistance in the opportunistic pathogen is partly caused by biofilms forming a physical barrier to antibiotic penetration. Here we focused on modifying tetravalent glycopeptide dendrimer ligands of lectins LecB or LecA to increase their biofilm inhibition activity. First heteroglycoclusters were investigated displaying one pair each of LecB specific fucosyl groups and LecA specific galactosyl groups and binding simultaneously to both lectins, one of which gave the first fully resolved crystal structure of a peptide dendrimer as LecB complex providing a structural model for dendrimer-lectin interactions (PDB ; 5D2A). Biofilm inhibition was increased by introducing additional cationic residues in these dendrimers but resulted in bactericidal effects similar to those of non-glycosylated polycationic antimicrobial peptide dendrimers. In a second approach dendrimers displaying four copies of the natural LecB ligand Lewis were prepared leading to slightly stronger LecB binding and biofilm inhibition. Finally synergistic application of a LecB specific non-bactericidal antibiofilm dendrimer with the antibiotic tobramycin at sub-inhibitory concentrations of both compounds allowed effective biofilm inhibition and dispersal.

PubMed: 29896342
DOI: 10.1039/c5sc03635f

実験手法

X-RAY DIFFRACTION (2.134 Å)