7fio

LecA from Pseudomonas aeruginosa in complex with a synthetic monovalent galactosidic inhibitor

spinqualitylabelsall models 7fio, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7fio is a 4 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: 4VH, CA, EDO 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 Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate-binding proteins are central to the initial and later persistent infection processes, i. e. bacterial adhesion and biofilm formation. The biofilm matrix is a major resistance determinant and protects the bacteria against external threats such as the host immune system or antibiotic treatment. Therefore, the development of drugs against the P. aeruginosa biofilm is of particular interest to restore efficacy of antimicrobials. Carbohydrate-based inhibitors for LecA and LecB were previously shown to efficiently reduce biofilm formations. Here, we report a new approach for inhibiting LecA with synthetic molecules bridging the established carbohydrate-binding site and a central cavity located between two LecA protomers of the lectin tetramer. Inspired by in silico design, we synthesized various galactosidic LecA inhibitors with aromatic moieties targeting this central pocket. These compounds reached low micromolar affinities, validated in different biophysical assays. Finally, X-ray diffraction analysis revealed the interactions of this compound class with LecA. This new mode of action paves the way to a novel route towards inhibition of P. aeruginosa biofilms. Targeting the Central Pocket of the Pseudomonas aeruginosa Lectin LecA.,Siebs E, Shanina E, Kuhaudomlarp S, da Silva Figueiredo Celestino Gomes P, Fortin C, Seeberger PH, Rognan D, Rademacher C, Imberty A, Titz A Chembiochem. 2022 Feb 4;23(3):e202100563. doi: 10.1002/cbic.202100563. Epub 2021 , Dec 2. PMID:34788491 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Galactose-binding lectin

Proteopedia Page Contributors and Editors (what is this?)

OCA