7oc7

LasB, alpha-alkyl-N-aryl mercaptoacetamide

spinqualitylabelsall models 7oc7, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7oc7 is a 1 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 1.95Å Ligands: CA, V85, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ELAS_PSEAE Cleaves elastin, collagen, IgG, and several complement components. Involved in the pathogenesis of P.aeruginosa infections. Publication Abstract from PubMed Extracellular virulence factors have emerged as attractive targets in the current antimicrobial resistance crisis. The Gram-negative pathogen Pseudomonas aeruginosa secretes the virulence factor elastase B (LasB), which plays an important role in the infection process. Here, we report a sub-micromolar, non-peptidic, fragment-like inhibitor of LasB discovered by careful visual inspection of structural data. Inspired by the natural LasB substrate, the original fragment was successfully merged and grown. The optimized inhibitor is accessible via simple chemistry and retained selectivity with a substantial improvement in activity, which can be rationalized by the crystal structure of LasB in complex with the inhibitor. We also demonstrate an improved in vivo efficacy of the optimized hit in Galleria mellonella larvae, highlighting the significance of this class of compounds as promising drug candidates. Substrate-Inspired Fragment Merging and Growing Affords Efficacious LasB Inhibitors.,Kaya C, Walter I, Yahiaoui S, Sikandar A, Alhayek A, Konstantinovic J, Kany AM, Haupenthal J, Kohnke J, Hartmann RW, Hirsch AKH Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112295. doi:, 10.1002/anie.202112295. Epub 2021 Dec 13. PMID:34762767 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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