4k47 | pdb_00004k47

Structure of the Streptococcus pneumoniae leucyl-tRNA synthetase editing domain bound to a benzoxaborole-AMP adduct

spinqualitylabelsall models 4k47, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4k47 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. Ligands: SO4, WMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SYL_STRPJ Publication Abstract from PubMed Streptococcus pneumoniae causes bacterial pneumonia with high mortality and morbidity. The emergency of multidrug-resistant bacteria threatens the treatment of the disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in cellular translation and is an attractive drug target for antimicrobial development. Here we report the compound ZCL039, a benzoxaborole-based derivative of AN2690, as a potent anti-pneumococcal agent that inhibits S. pneumoniae LeuRS (SpLeuRS) activity. We show using kinetic, biochemical analyses combined with the crystal structure of ZCL039-AMP in complex with the separated SpLeuRS editing domain, that ZCL039 binds to the LeuRS editing active site which requires the presence of tRNA(Leu), and employs an uncompetitive inhibition mechanism. Further docking models establish that ZCL039 clashes with the eukaryal/archaeal specific insertion I4ae helix within editing domains. These findings demonstrate the potential of benzoxaboroles as effective LeuRS inhibitors for pneumococcus infection therapy, and provide future structure-guided drug design and optimization. Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.,Hu QH, Liu RJ, Fang ZP, Zhang J, Ding YY, Tan M, Wang M, Pan W, Zhou HC, Wang ED Sci Rep. 2013 Aug 20;3:2475. doi: 10.1038/srep02475. PMID:23959225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminoacyl tRNA synthetase 3D structures

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