Identification of elongation factor 2 as the essential protein targeted by sordarins in Candida albicans.
The target for sordarins in Candida albicans has been elucidated. Kinetic experiments of sordarin inhibition as well as displacement experiments showed that the formation of a sordarin-target complex follows a reversible mechanism. Binding of tritiated drug to the target is enhanced in the presence of ribosomes. Isolation of the target by classical protein purification methods has allowed us to identify it as elongation factor 2. This is in agreement with the nature of sordarin derivatives as specific inhibitors of the elongation cycle within protein synthesis in yeasts.
Domínguez
J M
JM
Departamento de Investigación, Glaxo Wellcome S.A. 28760-Tres Cantos, Madrid, Spain.
Martín
J J
JJ
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000302:isolation & purification; D007192:Indenes; D008969:Molecular Sequence Data; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*
D000935:Antifungal Agents; D002352:Carrier Proteins; D007192:Indenes; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D011500:Protein Synthesis Inhibitors; C003329:sordarin