Tetracycline

Photoincorporation of tetracycline into Escherichia coli ribosomes. Identification of the major proteins photolabeled by native tetracycline and tetracycline photoproducts and implications for the inhibitory action of tetracycline on protein synthesis

“…Given the rigidity of the tRNA molecule, a substance which binds to the ribosome anywhere within the tRNA binding locus could, by preventing simultaneous two-site attachment, weaken tRNA binding to the ribosome and disrupt normal functioning of an aminoacyl-tRNA ribosome complex in protein synthesis. This is a plausible mechanism for the inhibitory action of TC and one which is in accord not only with the available evidence suggesting that TC has no direct competitive interaction with either the codon-anticodon site or the peptidyltransferase center (as summarized in Kaji, 1979;Gale et al, 1981) but also with the overlap between the position of S7 on the 30s subunit determined by immunoslectron microscopy (Lake, 1978) and the putative aminoacyl-tRNA binding locus ( Figure 7). Additional evidence for such an overlap is provided by the result of Ofengand (1980) that an aryl azide derivative of the 8-(4-thiouridine) base in Phe-tRNAPbe bound in the A site photo-cross-links to S19, a protein shown by immunoslectron microscopy to neighbor S7.…”

“…In this paper we develop a methodology for determining the contribution that native TC makes to the observed labeling pattern and show that the major protein photolabeled by native TC is S7. TC is known to inhibit aminoacyl-tRNA binding to the ribosome at the so-called A site (Kaji, 1979;Gale et al, 1981), and the current prevailing view (Strel'tsov et al, 1975;Tritton, 1977) is that such inhibition is a consequence of TC binding 16 h; 3-10 ,4260 units, SW 50 rotor, 45000 rpm, 135 min. When vertical rotors were utilized, following Winkelman & Kahan (1979), 70s ribosomes were layered over 100 pL of 7.5% sucrose which had itself been layered over a 15-30% sucrose gradient made up in TMKNa buffer.…”

Reconstitution of Escherichia coli ribosomes containing puromycin-modified S14: functional effects of the photoaffinity labeling of a protein essential for tRNA binding

“…The effect is more pronounced for 30s subunits (S14* restores 3%-5% of the binding restored by native S14- Table I) than for 70s ribosomes (S14* restores 15% of the binding restored by native S 14- Table 11). Furthermore, assuming to a first approximation that 30 pM tetracycline blocks almost all tRNA binding to the A site of 70s ribosomes but has little effect on binding to the P site (Kaji & Ryoji, 1979;Gale et al, 1981;Hasan et al, 1985) S14* restores 25% of the A-site binding restored by native S14 but restores none of the P-site binding (Table 11).…”

Mechanism of Action of Dipropofol and Synergistic Action with Other Antibacterial Agents in Vitro

“…No positive synergistic activity was observed with other seven antibiotics, when used carbenicillin, ampicillin and vancomycin (inhibitors of cell wall biosynthesis), 14,15) norfloxacin (an inhibitor of DNA gyrase), 16) and kanamycin (an inhibitor of protein synthesis), 17) erythromycin, tetracycline and chloramphenicol (inhibitors of protein synthesis different from kanamycin). [18][19][20] However, whether the inhibition of protein synthesis or amino acid incorporation by dipropofol is the primary site of action or a secondary one remains a problem. In the present study, the combination of dipropofol and rifampicin to treat VRE highlights novel drug targets and has importance in the design of new therapeutic regimes against resistant pathogens.…”