4lkd

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

spinqualitylabelsall models 4lkd, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lkd is a 16 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.307Å Ligands: CA, GAL, PHB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PA1L_PSEAE D-galactose specific lectin. Binds in decreasing order of affinity: melibiose, methyl-alpha-D-galactoside, D-galactose, methyl-beta-D-galactoside, N-acetyl-D-galactosamine. Similar to plant lectins in its selective (carbohydrate-specific) hemagglutinating activity. Publication Abstract from PubMed The galactopeptide dendrimer GalAG2 ((beta-Gal-OC6 H4 CO-Lys-Pro-Leu)4 (Lys-Phe-Lys-Ile)2 Lys-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 (KD )=2.7 muM) and GalA-KRL (KD =2.7 muM), 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 ((beta-Gal-OC6 H4 CO-Lys-Pro-Tyr)4 (Lys-Phe-Lys-Ile)2 Lys-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. Structure-Based Optimization of the Terminal Tripeptide in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting LecA.,Kadam RU, Bergmann M, Garg D, Gabrieli G, Stocker A, Darbre T, Reymond JL Chemistry. 2013 Dec 9;19(50):17054-63. doi: 10.1002/chem.201302587. Epub 2013 Nov, 4. PMID:24307364 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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