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23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22.

23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Research Abstract Details 

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  • 23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Abstract Text:

    rita berisioRita Berisio,natascia cortiNatascia Corti,peter pfisterPeter Pfister,ada yonathAda Yonath,erik c Erik C ,

    Resistance to macrolides and ketolides occurs mainly via alterations in RNA moieties of the drug-binding site. Using an A2058G mutant of Mycobacterium smegmatis, additional telithromycin resistance was acquired via deletion of 15 residues from protein L22. Molecular modeling, based on the crystal structure of the large ribosomal subunit from Deinococcus radiodurans complexed with telithromycin, shows that the telithromycin carbamate group is located in the proximity of the tip of the L22 hairpin-loop, allowing for weak interactions between them. These weak interactions may become more important once the loss of A2058 interactions destabilizes drug binding, presumably resulting in a shift of the drug toward the other side of the tunnel, namely, to the vicinity of L22. Hence, the deletion of 15 residues from L22 may further destabilize telithromycin binding and confer telithromycin resistance. Such deletions may also lead to notable differences in the tunnel outline, as well as to an increase of its diameter to a size, allowing the progression of the nascent chain.

    23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Publishing Authors By Initials

    r berisioR Berisio,n cortiN Corti,p pfisterP Pfister,a yonathA Yonath,ec EC ,

    For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research

    PUBMED ID PMID:

    MEDLINE DATE:

    23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Antimicrobial agents and chemotherapy

    VOLUME: 50

    Page Numbers: 3816-23

    Journal Abbreviation: Antimicrob. Agents Chemother.

    ISSN: 0066-4804

    DAY: 21

    MONTH: 08

    YEAR: 2006

    23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 315061

    23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Keywords Mesh Terms:

    KEYWORDS: Structure-Activity Relationship

    MESH TERMS: physiology

    Chemical & Substance for Abstract: 23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Information

    Substance Name: telithromycin

    Registry Number: 0

    Grant and Affiliation Information for 23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22.

    AFFILIATION: Department for Structural Biology, Weizmann Institute of Science, Rehovot, Israel. ada.yonath@weizmann.ac.il

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIGMS

    GRANT: GM34360

    ACRONYM: GM

    MEDLINETA: Antimicrob Agents Chemother

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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