Inhibition of bacterial IF2 binding to fMet-tRNA((fMet)) by aminoglycosides.
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.
Evans
J M
JM
Global High Throughput Screening, Pharmacia Corp., Kalamazoo, MI 49007, USA.
Turner
B A
BA
Bowen
S
S
Ho
A M
AM
Sarver
R W
RW
Benson
E
E
Parker
C N
CN
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*
D000900:Anti-Bacterial Agents; D039881:Prokaryotic Initiation Factor-2; D012358:RNA, Transfer, Met; C089238:fMet-tRNA(fMet); D007612:Kanamycin; D000583:Amikacin