7bzj

The Discovery of Benzhydrol-Oxaborole Hybrid Derivatives as Leucyl-tRNA Synthetase Inhibitors

spinqualitylabelsall models 7bzj, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7bzj is a 1 chain structure with sequence from Streptococcus pneumoniae ATCC 700669. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: FGX Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SYL_STRPJ Publication Abstract from PubMed Pneumonia caused by bacterium S. pneumoniae is a severe acute respiratory infectious disease with high morbidity and mortality, especially for children and immunity-compromised patients. The emergence of multidrug-resistant S. pneumoniae also presents a challenge to human health. Leucyl-tRNA synthetase (LeuRS) catalyzes the attachment of l-leucine to tRNA(Leu), which plays an essential role in protein translation and is considered an attractive antimicrobial drug target. In the present work, benzhydrol-oxaborole hybrid compounds were designed and synthesized as inhibitors of S. pneumoniae LeuRS. Exploration of the phenyl ring near Lysine 389 eventually yielded compounds 46 and 54 with submicromolar inhibitory potency. The co-crystal of compound 54 in the editing domain pocket of SpLeuRS was obtained and confirmed the formation of an additional hydrogen bond between the carbonyl of 54 and Lysine 389. It also showed anti-pneumococcal activity in vitro. The structure-activity relationship was discussed. This work will provide an essential foundation for the further development of anti-pneumococcal agents by targeting LeuRS. Discovery of benzhydrol-oxaborole derivatives as Streptococcus pneumoniae leucyl-tRNA synthetase inhibitors.,Hao G, Li H, Yang F, Dong D, Li Z, Ding Y, Pan W, Wang E, Liu R, Zhou H Bioorg Med Chem. 2020 Nov 13:115871. doi: 10.1016/j.bmc.2020.115871. PMID:33221064 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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