Heat and ionic limitations do not change the inhibition pattern of ribosomal peptidyltransferase by aminohexosyl-cytosine nucleoside antibiotics.
In a cell-free system derived from Escherichia coli, we investigated the inhibition of peptide bond formation by blasticidin S at 100 mM NH4+ and 5 degrees C or at 50 mM NH4+ and 25 degrees C. At both conditions, a transient phase of competitive inhibition is observed, followed by a mixed noncompetitive phase. The two phases of inhibition are compatible with a model in which a slow isomerization of the ribosome-drug complex occurs, as a result of ribosomal conformational changes. After this step, the mutually exclusive binding between acceptor substrate and antibiotic is converted to simultaneous binding. In comparison with a previous study carried out at 100 mM NH4+ and 25 degrees C, the present results demonstrate that the ribosomal conformational changes induced by blasticidin S can occur irrespectively of the reaction temperature and the ionic conditions.
Dinos
G P
GP
Department of Biochemistry, School of Medicine, University of Patras, Greece.
Kalpaxis
D L
DL
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006358:Hot Temperature; D007700:Kinetics; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors*; D011691:Puromycin / Q000737:chemistry / Q000494:pharmacology; D012270:Ribosomes / Q000187:drug effects / Q000201:enzymology*
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D009705:Nucleosides; D010455:Peptides; D011691:Puromycin; C004500:blasticidin S; D010458:Peptidyl Transferases