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4LKD

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

Summary for 4LKD
Entry DOI10.2210/pdb4lkd/pdb
Related4LKE 4LKF
DescriptorPA-I galactophilic lectin, peptide QRSA, beta-D-galactopyranose, ... (6 entities in total)
Functional Keywordslectin fold, sugar binding protein, galactose, sugar binding protein-inhibitor complex, sugar binding protein/inhibitor
Biological sourcePseudomonas aeruginosa
More
Cellular locationCytoplasm: Q05097
Total number of polymer chains16
Total formula weight108719.88
Authors
Kadam, R.U.,Stocker, A.,Reymond, J.-L. (deposition date: 2013-07-07, release date: 2013-12-18, Last modification date: 2024-11-06)
Primary citationKadam, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.307 Å)
Structure validation

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건을2024-12-18부터공개중

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