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Volume 147, Issue 2

Species-specific inhibition of fungal protein synthesis by sordarin: identification of a sordarin-specificity region in eukaryotic elongation factor 2

The GenBank accession numbers for the sequences reported in this manuscript are AF107286–AF107291, AF292693 and AF248644.

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Abstract

The sordarin class of natural products selectively inhibits fungal protein synthesis by impairing the function of eukaryotic elongation factor 2 (eEF2). Mutations in 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 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 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 expression of species eEF2s in and translation and growth inhibition assays using hybrid 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 identical to that observed with mammalian eEF2.

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Keyword(s): eEF2, eukaryotic elongation factor 2 , EF-G, prokaryotic elongation factor G , elongation , protein synthesis , sordarin specificity and translation
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2001-02-01
2024-04-25
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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.
Microbiology 147, 383 (2001); https://doi.org/10.1099/00221287-147-2-383
/content/journal/micro/10.1099/00221287-147-2-383
/content/journal/micro/10.1099/00221287-147-2-383
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