9rl1

APH(2)-IVa with an inhibitor

spinqualitylabelsall models 9rl1, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9rl1 is a 2 chain structure with sequence from Enterococcus casseliflavus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: A1JG8, DMS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O68183_ENTCA Publication Abstract from PubMed Antibiotic resistance is rapidly emerging as one of the most critical health threats, with resistant microorganisms progressively diminishing the effectiveness of established antibiotics. As a result, the development of therapeutic approaches that effectively target resistant pathogens is of utmost importance. In this study, we developed inhibitors for APH(2")-IVa, a bacterial kinase conveying resistance to aminoglycoside antibiotics. Starting from a hit of a fragment-based screening, we explored the inhibitory motif by structure-based design, ultimately leading to a series of triazole analogues. Advanced analogues displayed promising ADME properties, emerging selectivity vs a panel of human kinases, permeability in both Gram-positive and Gram-negative bacteria, and a moderate antibiotic efficacy for clinical strains of P. aeruginosa. Taken together, our results suggest inhibition of bacterial kinases could be a promising option to reinstall the efficacy of aminoglycoside antibiotics. Targeting bacterial kinases as a strategy to counteract antibiotic resistance.,Buffa V, Kowalewski J, Qi G, Deutscher R, Cica M, Richardoz M, Tomaszczyk M, Kramer A, Knapp S, Dunyach-Remy C, Rox K, Guichou JF, Lionne C, Hausch F Commun Chem. 2025 Dec 4;8(1):390. doi: 10.1038/s42004-025-01794-7. PMID:41345223 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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