7fjh

LecA from Pseudomonas aeruginosa in complex with 4-Phenylbutyryl hydroxamic acid (CAS: 32153-46-1)

spinqualitylabelsall models 7fjh, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7fjh 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 1.79Å Ligands: 4R9, CA 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 Carbohydrate-protein interactions are key for cell-cell and host-pathogen recognition and thus, emerged as viable therapeutic targets. However, their hydrophilic nature poses major limitations to the conventional development of drug-like inhibitors. To address this shortcoming, four fragment libraries were screened to identify metal-binding pharmacophores (MBPs) as novel scaffolds for inhibition of Ca(2+)-dependent carbohydrate-protein interactions. Here, we show the effect of MBPs on the clinically relevant lectins DC-SIGN, Langerin, LecA and LecB. Detailed structural and biochemical investigations revealed the specificity of MBPs for different Ca(2+)-dependent lectins. Exploring the structure-activity relationships of several fragments uncovered the functional groups in the MBPs suitable for modification to further improve lectin binding and selectivity. Selected inhibitors bound efficiently to DC-SIGN-expressing cells. Altogether, the discovery of MBPs as a promising class of Ca(2+)-dependent lectin inhibitors creates a foundation for fragment-based ligand design for future drug discovery campaigns. Targeting undruggable carbohydrate recognition sites through focused fragment library design.,Shanina E, Kuhaudomlarp S, Siebs E, Fuchsberger FF, Denis M, da Silva Figueiredo Celestino Gomes P, Clausen MH, Seeberger PH, Rognan D, Titz A, Imberty A, Rademacher C Commun Chem. 2022 May 20;5(1):64. doi: 10.1038/s42004-022-00679-3. PMID:36697615 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Galactose-binding lectin

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