Biochemical study of minosaminomycin in relation to the kasugamycin group antibiotics.
Minosaminomycin is structurally related to kasugamycin and inhibits protein synthesis in mycobacteria. It also inhibits phage f2 RNA-directed protein synthesis in a cell-free system of Escherichia coli by 50% at 2 x 10(-7) M. It is 100-times more potent than kasugamycin in this system. At 10(-7) M minosaminomycin inhibits EF-T dependent binding of aminoacyl-tRNA to ribosomes by 50%. This effect is markedly diminished if minosaminomycin is added to the assay system after a brief incubation of ribosomes with mRNA. Like kasugamycin, minosaminomycin preferentially inhibits the initiation of protein synthesis directed by phage f2 RNA in vitro and does not cause miscoding. Ribosomes from kasugamycin-resistant mutants Ksg A and Ksg C were as sensitive to minosaminomycin as those from each parent strain. In spite of the strong inhibitory activity of minosaminomycin manifested in cell-free systems of E. coli, this compound inhibits the growth of the organism itself only slightly. This discrepancy could be ascribed to impermeability, as E. coli cells with modified permeability show greater sensitivity to minosaminomycin. There is no indication that the antibiotic is activated in E. coli cells. On the basis of these results, the structural features of these antibiotics is inactivated in E. coli cells. On the basis of these results, the structural features of these antibiotics essential for interaction with ribosomes and for permeability into the cells are discussed.
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002463:Cell Membrane Permeability; D002474:Cell-Free System / Q000187:drug effects; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D046911:Macromolecular Substances / Q000096:biosynthesis; D009161:Mycobacterium / Q000378:metabolism*; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D046911:Macromolecular Substances; D007294:Inositol; D012343:RNA, Transfer