4OX9

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

Summary for 4OX9

• Entry DOI: 10.2210/pdb4ox9/pdb
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (25 entities in total)
• Functional Keywords: protein biosynthesis, ribosome, rna, 30s, 16s, ribosomal subunit, aminoglycoside, a1408, methyltransferase, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Escherichia coli; More
• Total number of polymer chains: 22
• Total formula weight: 807959.84

Authors

Dunkle, J.A.,Conn, G.L.,Dunham, C.M. (deposition date: 2014-02-04, release date: 2014-04-09, Last modification date: 2023-09-27)

Primary citation

Dunkle, J.A.,Vinal, K.,Desai, P.M.,Zelinskaya, N.,Savic, M.,West, D.M.,Conn, G.L.,Dunham, C.M.
Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA.
Proc.Natl.Acad.Sci.USA, 111:6275-6280, 2014

PubMed Abstract: 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 m(1)A1408 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.

PubMed: 24717845
DOI: 10.1073/pnas.1402789111

Experimental method

X-RAY DIFFRACTION (3.8035 Å)