ABSTRACT
M a n y antibiotic s ar e inhibitor s o f protei n biosynthesis , an d i n man y instance s
their mechanisms o f actio n is k n o wn (Tabl e 12.3). Th e clinically useful antibiotic s
are thos e tha t ar e activ e agains t prokaryote s an d hav e littl e i f an y effec t o n
eukaryotic protei n biosynthesis . Inhibitor s other tha n antibiotic s includ e diphthe-
ria toxin, w h i c h inhibits protein biosynthesis b y modifyin g th e eukaryoti c elonga -
tion facto r E F - 2 . Th e toxin interact s wi t h a recepto r o n th e surfac e o f a sensitiv e
cell an d i s proteolyticall y cleave d t o yiel d tw o fragments , a n A fragmen t an d a B
fragment. Th e B fragmen t facilitate s th e penetratio n o f th e A fragmen t throug h
the cel l membrane . Th e A fragmen t catalyze s th e A D P ribosylatio n o f a singl e
unusua l amin o residu e presen t i n E F - 2 (diphthamide), w h i c h i s forme d b y
posttranslational modificatio n o f histidin e (Figur e 12.4) . Thi s A D P ribosylatio n
irreversibly block s th e capacit y o f E F - 2 to carr y ou t th e translocatio n ste p o f
protein chai n elongation . A singl e molecul e o f th e A fragmen t ca n kil l th e cell .
The functio n o f diphthamid e i n E F - 2 i s u n k n o w n , bu t i t i s clearl y critical .
