A noncanonical binding site of chloramphenicol revealed via molecular dynamics simulations.

Autor: Makarov GI; South Ural State University, 454080 Chelyabinsk, Russia. Electronic address: makarovgi@susu.ru., Makarova TM; South Ural State University, 454080 Chelyabinsk, Russia; Lomonosov Moscow State University, Faculty of Chemistry, 119991 Moscow, Russia.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2018 Dec; Vol. 1862 (12), pp. 2940-2947. Date of Electronic Publication: 2018 Sep 22.
DOI: 10.1016/j.bbagen.2018.09.012
Abstrakt: Chloramphenicol, an antibiotic belonging to the family of amphenicols, is an inhibitor of translation. On the basis of X-ray structural analysis of the binding of chloramphenicol to free bacterial ribosomes, the chloramphenicol action mechanism that consists in preventing the binding of aminoacyl-tRNA to the A-site of the large subunit of the ribosome was adopted. However, the known structures of chloramphenicol complexes with bacterial ribosomes poorly explain the results of the experiments on the chemical modification of 23S rRNA, the resistance to chloramphenicol caused by mutations in 23S rRNA and, which is particularly important, the selectivity of chloramphenicol in suppression of translation, depending on the amino acid sequence of the nascent peptide. In the present study the putative structure of the chloramphenicol complex with a bacterial ribosome in the A,A/P,P-state has been obtained by molecular dynamics simulations methods. The proposed structure of the complex allows us to explain the results of biochemical studies of the interaction of chloramphenicol with the bacterial ribosome.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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