Table 1.

Inhibitors of Ribosomal Translocation

Inhibitor	Domain of Life	Mechanism
Aminoglycosides (gentamycin, hygromycin B, kanamycin, neomycin, paromomycin)	B, A, E	Aminoglycosides inhibit both EF‐G‐induced and spontaneous translocation by increasing the affinity of peptidyl‐tRNA to the A site.22
Spectinomycin	B, A	Spectinomycin is thought to inhibit translocation by interfering with swiveling of the head of the small ribosomal subunit.22
Tuberactinomycins (viomycin and capreomycin)	B	Viomycin and capreomycin inhibit both EF‐G‐induced and spontaneous translocation by increasing the affinity of peptidyl‐tRNA to the A site and locking the ribosome in the rotated hybrid state.20, 25, 26
Pactamycin	B, A, E	Pactamycin inhibits translocation by occluding the mRNA‐binding channel in the E site of the small ribosomal subunit.27, 28
Thiostrepton	B, A	Thiostrepton inhibits binding of EF‐G to the ribosome.26, 29, 30
Fusidic acid	B, A, E	Fusidic acid inhibits EF‐G/EF‐2 release after GTP hydrolysis.31
Sordarin	E(fungi)	Inhibits EF‐2 release from the ribosome after GTP hydrolysis.32
EF‐2 kinase	E	EF‐2 kinase phosphorylates a conserved threonine residue (Thr 56 in human EF‐2) in domain I of EF‐2, which hampers EF‐2 binding to the ribosome.33
Diphtheria toxin	E(human)	Diphtheria toxin abrogates EF‐2 activity by catalyzing ADP‐ribosylation of the diphtamide residue (i.e. posttranslationallly‐modified His714 in human EF‐2).34
α‐sarcin and ricin‐like ribotoxins	B, A, E	These ribotoxins can cleave (α‐sarcin) or depurinate (ricin) the SRL of the rRNA of the large subunit, which activates GTPase activity of EF‐G (EF‐2) and EF‐Tu (EF‐1A).22

The column ‘Domain of life’ indicates whether the translocation inhibitors are active in bacteria (B), archaea (A) or eukaryotes (E).