A noncanonical binding site of chloramphenicol revealed via molecular dynamics simulations
Autor: | T. M. Makarova, G. I. Makarov |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
medicine.drug_class Protein subunit Biophysics Molecular Conformation Molecular Dynamics Simulation 01 natural sciences Biochemistry Ribosome 03 medical and health sciences RNA Transfer 23S ribosomal RNA 0103 physical sciences Drug Resistance Bacterial medicine Amino Acid Sequence Binding site Molecular Biology Peptide sequence Binding Sites 010304 chemical physics Chemistry Chloramphenicol Translation (biology) Anti-Bacterial Agents Molecular Docking Simulation RNA Ribosomal 23S 030104 developmental biology Mutation Peptides Amphenicols Ribosomes medicine.drug |
Zdroj: | Biochimica et biophysica acta. General subjects. 1862(12) |
ISSN: | 1872-8006 |
Popis: | 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. |
Databáze: | OpenAIRE |
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