The dynamic structure of EF-G studied by fusidic acid resistance and internal revertants

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Bibtex

@article{d04204ce470c464e80225d048f843474,
title = "The dynamic structure of EF-G studied by fusidic acid resistance and internal revertants",
abstract = "We have previously identified 20 different fusidic acid-resistant alleles of fusA, encoding mutant forms of the ribosomal translocase EF-G. One of these, P413L, is used here as the starting point in selections for internal revertants, identifying 20 different pseudo-wild-type forms of EF-G. We have also identified two alleles of fusA previously isolated as suppressors of 4.5 S RNA deficiency. All of these mutants are analysed in terms of their effects on the structural dynamics of EF-G. Most mutation conferring fusidic acid-resistance interfere with conformational changes of EF-G, but some may be located at a possible fusidic acid binding site. Revertants of the P413L mutations restore the function of EF-G with or without affecting the level of resistance to fusidic acid. The revertant mutations probably restore the balance between the GDP and GTP conformations of EF-G off the ribosome, and most of them are located close to the interface between the G domain and domain II. The procedure for the isolation of pseudo-wild-type forms of EF-G can be used to direct evolution progressively away from the wild-type while still maintaining the essential functions of EF-G.",
keywords = "Anti-Bacterial Agents, Binding Sites, DNA Mutational Analysis, Directed Molecular Evolution, Drug Resistance, Microbial, Escherichia coli, Fusidic Acid, Models, Molecular, Mutation, Peptide Elongation Factor G, Peptide Elongation Factors, Protein Structure, Tertiary, Protein Synthesis Inhibitors, RNA, Ribosomal, Salmonella typhimurium, Spectinomycin, Suppression, Genetic, Thermus thermophilus, Journal Article, Research Support, Non-U.S. Gov't",
author = "U Johanson and A Aevarsson and A Liljas and D Hughes",
year = "1996",
month = "5",
day = "10",
doi = "10.1006/jmbi.1996.0259",
language = "English",
volume = "258",
pages = "420--32",
journal = "Journal of Molecular Biology",
issn = "1089-8638",
publisher = "Elsevier",
number = "3",

}