6qom | pdb_00006qom

Crystal structure of TrmD, a tRNA-(N1G37) methyltransferase, from Mycobacterium abscessus in complex with Fragment 16 (2-Amino-3-nitropyridine)

spinqualitylabelsall models 6qom, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qom is a 2 chain structure with sequence from "mycobacterium_abcessus"_moore_and_frerichs_1953 "mycobacterium abcessus" moore and frerichs 1953. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: JBE Related: 6nvr Gene: trmD, MAB_3226c ("Mycobacterium abcessus" Moore and Frerichs 1953) Activity: tRNA (guanine(37)-N(1))-methyltransferase, with EC number 2.1.1.228 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [B1MDI3_MYCA9] Specifically methylates guanosine-37 in various tRNAs.[HAMAP-Rule:MF_00605][RuleBase:RU003464][SAAS:SAAS00040552] Publication Abstract from PubMed Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. Fragment library screening, followed by structure-guided chemical elaboration of hits, led to the rapid development of drug-like molecules with potent in vitro TrmD inhibitory activity. Several of these compounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential as the basis for a novel class of broad-spectrum mycobacterial drugs. Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification.,Thomas SE, Whitehouse AJ, Brown K, Burbaud S, Belardinelli JM, Sangen J, Lahiri R, Libardo MDJ, Gupta P, Malhotra S, Boshoff HIM, Jackson M, Abell C, Coyne AG, Blundell TL, Floto RA, Mendes V Nucleic Acids Res. 2020 Jun 30. pii: 5865065. doi: 10.1093/nar/gkaa539. PMID:32602532 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also TRNA methyltransferase 3D structures

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