Fungal translation machinery

The fungal translation machinery is a complex of ribonucleoproteins and specialized enzymes responsible for the synthesis of all fungal proteins, making it essential for the growth, replication, and survival of fungal pathogens. This machinery consists of the 80S ribosome (comprising 60S and 40S subunits) and several soluble translation factors, including elongation factors eEF1, eEF2, and the fungus-specific eEF3. Because protein synthesis is a fundamental life process, inhibitors of this machinery can exert potent fungicidal or fungistatic effects. Drugs like tavaborole target specific enzymes within this pathway, such as leucyl-tRNA synthetase, by trapping tRNA in the enzyme's editing site to halt protein production. Other agents, such as the sordarin class, target elongation factor 2 (eEF2) to prevent the translocation step of the ribosome. While many components of the translation apparatus are conserved between fungi and humans, therapeutic utility relies on targeting unique fungal structural motifs or factors like eEF3 that are absent in mammalian cells. This target is clinically significant in treating a wide range of infections, including onychomycosis and systemic candidiasis.

Other names

Fungal protein synthesisFungal ribosomeFungal protein synthesis pathwayFungal translation apparatusFungal 80S ribosome

Inhibition of fungal protein synthesis through various molecular mechanisms including: (1) the inhibition of aminoacyl-tRNA synthetases (e.g., leucyl-tRNA synthetase) via the formation of a stable tRNA-adduct in the editing site, preventing tRNA charging; (2) the blockade of translation elongation factors such as eEF2, which halts ribosome translocation; and (3) the specific inhibition of fungal-unique factors like eEF3, which prevents the ribosome-dependent ATPase and GTPase activities required for uncharged tRNA release and ternary complex binding.