| http://purl.uniprot.org/citations/22767604 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22767604 | http://www.w3.org/2000/01/rdf-schema#comment | "Antibiotic resistance in bacteria is often associated with fitness loss, which is compensated by secondary mutations. Fusidic acid (FA), an antibiotic used against pathogenic bacteria Staphylococcus aureus, locks elongation factor-G (EF-G) to the ribosome after GTP hydrolysis. To clarify the mechanism of fitness loss and compensation in relation to FA resistance, we have characterized three S. aureus EF-G mutants with fast kinetics and crystal structures. Our results show that a significantly slower tRNA translocation and ribosome recycling, plus increased peptidyl-tRNA drop-off, are the causes for fitness defects of the primary FA-resistant mutant F88L. The double mutant F88L/M16I is three to four times faster than F88L in both reactions and showed no tRNA drop-off, explaining its fitness compensatory phenotype. The M16I mutation alone showed hypersensitivity to FA, higher activity, and somewhat increased affinity to GTP. The crystal structures demonstrate that Phe-88 in switch II is a key residue for FA locking and also for triggering interdomain movements in EF-G essential for its function, explaining functional deficiencies in F88L. The mutation M16I loosens the hydrophobic core in the G domain and affects domain I to domain II contact, resulting in improved activity both in the wild-type and F88L background. Thus, FA-resistant EF-G mutations causing fitness loss and compensation operate by affecting the conformational dynamics of EF-G on the ribosome."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.378521"xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/author | "Selmer M."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/author | "Koh C.S."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/author | "Sanyal S."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/author | "Peisker K."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/author | "Koripella R.K."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/pages | "30257-30267"xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/title | "Mechanism of elongation factor-G-mediated fusidic acid resistance and fitness compensation in Staphylococcus aureus."xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://purl.uniprot.org/core/volume | "287"xsd:string |
| http://purl.uniprot.org/citations/22767604 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22767604 |
| http://purl.uniprot.org/citations/22767604 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22767604 |
| http://purl.uniprot.org/uniprot/#_P68790-mappedCitation-22767604 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22767604 |
| http://purl.uniprot.org/uniprot/P68790 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/22767604 |