title: ÐÐ¾Ð»ÐµÐºÑÐ»ÑÑÐ½ÑÐ¹ Ð¼ÐµÑ Ð°Ð½Ð¸Ð·Ð¼ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ñ ÑÑÐ°Ð½ÑÐ»ÑÑÐ¸Ð¸ Ð°Ð½ÑÐ¸Ð±Ð¸Ð¾ÑÐ¸ÐºÐ¾Ð¼ Ð°Ð¼Ð¸ÐºÑÐ¼Ð°ÑÐ¸Ð½Ð¾Ð¼ Ð
title: Ð½Ð°ÑÑÐ½ÑÐ¹ Ð´Ð¾ÐºÐ»Ð°Ð´
titleType: Subtitle
title: The molecular mechanism of inhibition of translation by the antibiotic amicoumacin A
Creators: name: ÐÐ°ÐºÑÐ¸Ð¼Ð¾Ð²Ð°, ÐÐ»ÐµÐ½Ð°
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2018
Subjects: ÐÐ½ÑÐ¸Ð±Ð¸Ð¾ÑÐ¸ÐºÐ¸
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description: Amicoumacin A belongs to the group of isocoumarin antibiotics and has a strong antimicrobial activity. Recently it was shown, that the antibiotic binds at the E site of the 30S ribosome subunit, forming contacts with the nucleotides of 16S rRNA and mRNA at the start codon region. In this study, it is shown that the main step of translation inhibited by amicoumacin A is translocation. At this step, the antibiotic decreases the rate of peptidyl-tRNA movement from the A to P site of the ribosome and hampers the functional activity of the ribosome. Translocation reaction was studied by means of pre-steady state kinetics, including reactions inhibited by antibiotics, with partially ASF-shortened ribosomes. Functional activities of elongation factors G from mesophilic and thermophilic bacteria was studied. In addition, this work also reveals the mechanism of resistance to the antibiotic by specific aminoacid substitutions (G542V or G581A) or insertion (ins544K) in the elongation factor EF-G.