4LKD

Crystal Structure of Pseudomonas aeruginosa Lectin LecA Complexed with GalA-QRS at 2.31 A Resolution

4LKD の概要

• エントリーDOI: 10.2210/pdb4lkd/pdb
• 関連するPDBエントリー: 4LKE 4LKF
• 分子名称: PA-I galactophilic lectin, peptide QRSA, beta-D-galactopyranose, ... (6 entities in total)
• 機能のキーワード: lectin fold, sugar binding protein, galactose, sugar binding protein-inhibitor complex, sugar binding protein/inhibitor
• 由来する生物種: Pseudomonas aeruginosa; 詳細
• 細胞内の位置: Cytoplasm: Q05097
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 108719.88

構造登録者

Kadam, R.U.,Stocker, A.,Reymond, J.-L. (登録日: 2013-07-07, 公開日: 2013-12-18, 最終更新日: 2024-11-06)

主引用文献

Kadam, R.U.,Bergmann, M.,Garg, D.,Gabrieli, G.,Stocker, A.,Darbre, T.,Reymond, J.-L.
Structure-Based Optimization of the Terminal Tripeptide in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting LecA.
Chemistry, 19:17054-17063, 2013

PubMed Abstract: The galactopeptide dendrimer GalAG2 ((β-Gal-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2) binds strongly to the Pseudomonas aeruginosa (PA) lectin LecA, and it inhibits PA biofilms, as well as disperses already established ones. By starting with the crystal structure of the terminal tripeptide moiety GalA-KPL in complex with LecA, a computational mutagenesis study was carried out on the galactotripeptide to optimize the peptide-lectin interactions. 25 mutants were experimentally evaluated by a hemagglutination inhibition assay, 17 by isothermal titration calorimetry, and 3 by X-ray crystallography. Two of these tripeptides, GalA-KPY (dissociation constant (K(D))=2.7 μM) and GalA-KRL (K(D)=2.7 μM), are among the most potent monovalent LecA ligands reported to date. Dendrimers based on these tripeptide ligands showed improved PA biofilm inhibition and dispersal compared to those of GalAG2, particularly G2KPY ((β-Gal-OC6H4CO-Lys-Pro-Tyr)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2). The possibility to retain and even improve the biofilm inhibition in several analogues of GalAG2 suggests that it should be possible to fine-tune this dendrimer towards therapeutic use by adjusting the pharmacokinetic parameters in addition to the biofilm inhibition through amino acid substitutions.

PubMed: 24307364
DOI: 10.1002/chem.201302587

実験手法

X-RAY DIFFRACTION (2.307 Å)