RT Journal Article SR Electronic(1) A1 Shastry, Mythili A1 Nielsen, Jennifer A1 Ku, Theresa A1 Hsu, Ming-Jo A1 Liberator, Paul A1 Anderson, Jennifer A1 Schmatz, Dennis A1 Justice, Michael C.YR 2001 T1 Species-specific inhibition of fungal protein synthesis by sordarin: identification of a sordarin-specificity region in eukaryotic elongation factor 2The GenBank accession numbers for the sequences reported in this manuscript are AF107286–AF107291, AF292693 and AF248644. JF Microbiology, VO 147 IS 2 SP 383 OP 390 DO https://doi.org/10.1099/00221287-147-2-383 PB Microbiology Society, SN 1465-2080, AB The sordarin class of natural products selectively inhibits fungal protein synthesis by impairing the function of eukaryotic elongation factor 2 (eEF2). Mutations in Saccharomyces cerevisiae eEF2 or the ribosomal stalk protein rpP0 can confer resistance to sordarin, although eEF2 is the major determinant of sordarin specificity. It has been shown previously that sordarin specifically binds S. cerevisiae eEF2 while there is no detectable binding to eEF2 from plants or mammals, despite the high level of amino acid sequence conservation among these proteins. In both whole-cell assays and in vitro translation assays, the efficacy of sordarin varies among different species of pathogenic fungi. To investigate the basis of sordarin’s fungal selectivity, eEF2 has been cloned and characterized from several sordarin-sensitive and -insensitive fungal species. Results from in vivo expression of Candida species eEF2s in S. cerevisiae and in vitro translation and growth inhibition assays using hybrid S. cerevisiae eEF2 proteins demonstrate that three amino acid residues within eEF2 account for the selectivity of this class of compounds. It is also shown that the corresponding residues at these positions in human eEF2 are sufficient to confer sordarin insensitivity to S. cerevisiae identical to that observed with mammalian eEF2., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/00221287-147-2-383