FIGURE 1: Potential role of yeast KTI13 in diphthamide modification. (A) Simplified pathway overview [24][25]. Diphthamide synthesis initiates with modifcation of EF2 at His-699 by ACP involving proteins Dph1-Dph4. Subsequential reactions to convert ACP into end product diphthamide entail Dph5-Dph7. Potential Kti13 involvement in the synthesis steps is indicated (‘?’). Diphthamide can be hijacked by diphtheria toxin (DT) for ADP-ribosylation in an NAD+ fashion and induces cell death by EF2 inactivation (skull-crossbones). (B) KTI13 and DPH1 gene deletion strains resist against DT cytotoxicity. Yeast strains carrying pGAL-DT [39], a plasmid for galactose-inducible expression of the lethal ADP-ribosylase domain from DT (see A) were spotted onto medium containing 0.5-1% (w/v) galactose (gal) or 2% (w/v) glucose (glc). Following DT induction, growth inhibition of diphthamide-proficient wild-type is distinguishable from DT resistance of diphthamide-deficient dph1Δ and kti13Δ mutants (green arrows).

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