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Antimicrobial Agents and Chemotherapy, September 1998, p. 2279-2283, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of Elongation Factor 2 as the Essential Protein Targeted by Sordarins in Candida albicans

Juan Manuel Domínguez and J. Julio Martín*

Departamento de Investigación, Glaxo Wellcome S.A. 28760-Tres Cantos, Madrid, Spain

Received 26 January 1998/Returned for modification 22 April 1998/Accepted 24 June 1998

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.

* Corresponding author. Mailing address: Departamento de Investigación, Glaxo Wellcome S.A., C/Severo Ochoa 2, 28760-Tres Cantos, Madrid, Spain. Phone: 34 91 8070301. Fax: 34 91 8070595. E-mail: jjmp28182{at}GlaxoWellcome.co.uk.

Antimicrobial Agents and Chemotherapy, September 1998, p. 2279-2283, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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