4ox9

Crystal structure of the aminoglycoside resistance methyltransferase NpmA bound to the 30S ribosomal subunit

spinqualitylabelsall models 4ox9, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ox9 is a 22 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895 and Thermus thermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, SFG, ZN Gene: npmA ("Bacillus coli" Migula 1895) Activity: 16S rRNA (adenine(1408)-N(1))-methyltransferase, with EC number 2.1.1.180 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Aminoglycosides are potent, broad spectrum, ribosome-targeting antibacterials whose clinical efficacy is seriously threatened by multiple resistance mechanisms. Here, we report the structural basis for 30S recognition by the novel plasmid-mediated aminoglycoside-resistance rRNA methyltransferase A (NpmA). These studies are supported by biochemical and functional assays that define the molecular features necessary for NpmA to catalyze m1A1408 modification and confer resistance. The requirement for the mature 30S as a substrate for NpmA is clearly explained by its recognition of four disparate 16S rRNA helices brought into proximity by 30S assembly. Our structure captures a "precatalytic state" in which multiple structural reorganizations orient functionally critical residues to flip A1408 from helix 44 and position it precisely in a remodeled active site for methylation. Our findings provide a new molecular framework for the activity of aminoglycoside-resistance rRNA methyltransferases that may serve as a functional paradigm for other modification enzymes acting late in 30S biogenesis. Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA.,Dunkle JA, Vinal K, Desai PM, Zelinskaya N, Savic M, West DM, Conn GL, Dunham CM Proc Natl Acad Sci U S A. 2014 Apr 9. PMID:24717845 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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