5znk | pdb_00005znk

Crystal structure of a bacterial ProRS with ligands

spinqualitylabelsall models 5znk, resolution 2.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5znk is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.07Å Ligands: 9G3, ANP, GOL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Aminoacyl-tRNA synthetases (aaRSs) are promising antimicrobial targets due to their essential roles in protein translation, and expanding their inhibitory mechanisms will provide new opportunities for drug discovery. We report here that halofuginone (HF), an herb-derived medicine, moderately inhibits prolyl-tRNA synthetases (ProRSs) from various pathogenic bacteria. A cocrystal structure of Staphylococcus aureus ProRS (SaProRS) with HF and an ATP analog was determined, which guided the design of new HF analogs. Compound 3 potently inhibited SaProRS at IC(50) = 0.18 muM and K(d) = 30.3 nM and showed antibacterial activities with an MIC of 1-4 mug/mL in vitro. The bacterial drug resistance to 3 only developed at a rate similar to or slower than those of clinically used antibiotics in vitro. Our study indicates that the scaffold and ATP-aided inhibitory mechanism of HF could apply to bacterial ProRS and also provides a chemical validation for using bacterial ProRS as an antibacterial target. Structure-Guided Design of Halofuginone Derivatives as ATP-Aided Inhibitors Against Bacterial Prolyl-tRNA Synthetase.,Cheng B, Cai Z, Luo Z, Luo S, Luo Z, Cheng Y, Yu Y, Guo J, Ju Y, Gu Q, Xu J, Jiang X, Li G, Zhou H J Med Chem. 2022 Dec 8;65(23):15840-15855. doi: 10.1021/acs.jmedchem.2c01496. , Epub 2022 Nov 17. PMID:36394909 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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