title: The Pathogen-Derived Aminoglycoside Resistance 16S rRNA Methyltransferase NpmA Possesses Dual m1A1408/m1G1408 Specificity.
abstract: Chemical modification of 16S rRNA can confer exceptionally high-level resistance to a diverse set of aminoglycoside antibiotics. Here, we show that the pathogen-derived enzyme NpmA possesses dual m(1)A1408/m(1)G1408 activity, an unexpected property apparently unique among the known aminoglycoside resistance 16S rRNA (m(1)A1408) methyltransferases. Although the biological significance of this activity remains to be determined, such mechanistic variation in enzymes acquired by pathogens has significant implications for development of inhibitors of these emerging resistance determinants.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Zelinskaya
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Witek
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA gconn@emory.edu.
authors.forename: Graeme L
authors.identifier: http://orcid.org/0000-0002-2419-380X
authors.initials: GL
authors.lastname: Conn
mesh_terms: D039903:Actinobacteria / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D000068016:Eubacteriales / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007700:Kinetics; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D012336:RNA, Ribosomal, 16S; D008780:Methyltransferases; C554940:NpmA protein, E coli