title: Inhibition of bacterial IF2 binding to fMet-tRNA((fMet)) by aminoglycosides.
abstract: Screening for inhibitors of bacterial protein synthesis Initiation Factor 2 (IF2) binding to N-formyl-Methionyl-transfer RNA (fMet-tRNA((fMet))) identified a series of aminoglycosides, that included amikacin and kanamycin A1, as inhibitors of this interaction. Subsequent testing revealed that aminoglycosides displayed a wide range of inhibitory activity. However, the failure of these compounds to completely inhibit binding of IF2 to fMet-tRNA((fMet)), the known ability of aminoglycosides to bind RNA, and the ability of the aminoglycosides to displace PicoGreen bound to fMet-tRNA((fMet)) suggest these compounds act by binding fMet-tRNA((fMet)). This hypothesis is further supported by isothermal denaturation experiments that failed to show any interaction between the IF2 protein and the aminoglycosides.
authors.affiliation: Global High Throughput Screening, Pharmacia Corp., Kalamazoo, MI 49007, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Evans
authors.forename: B A
authors.initials: BA
authors.lastname: Turner
authors.forename: S
authors.initials: S
authors.lastname: Bowen
authors.forename: A M
authors.initials: AM
authors.lastname: Ho
authors.forename: R W
authors.initials: RW
authors.lastname: Sarver
authors.forename: E
authors.initials: E
authors.lastname: Benson
authors.forename: C N
authors.initials: CN
authors.lastname: Parker
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D007612:Kanamycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D039881:Prokaryotic Initiation Factor-2 / Q000187:drug effects / Q000378:metabolism*; D011489:Protein Denaturation; D012358:RNA, Transfer, Met / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D039881:Prokaryotic Initiation Factor-2; D012358:RNA, Transfer, Met; C089238:fMet-tRNA(fMet); D007612:Kanamycin; D000583:Amikacin