You are a visiting physician treating patients at a clinic in Bangladesh. Your current patient is a 5-year-old girl complaining of a fever and sore throat for the past week. Physical examination shows a gray-white membrane on the tonsils and the pharyngeal wall. A swab of the membranes is taken and an infectious agent is characterized. Your studies of a toxin purified from this infectious agent demonstrate that it markedly inhibits protein synthesis. Which of the following is most likely to be the mechanism by which this toxin exerts its activity?

Question

Quizplus · Accepted Answer

The toxin from Corynebacterium diphtheriae, which causes diphtheria, inhibits protein synthesis by inactivating elongation factor-2 (EF-2), thereby inhibiting the translocation step in protein chain elongation.  The child is most likely suffering from diphtheria. A protein from Corynebacterium diphtheria which causes diphtheria catalyzes the ADP-ribosylation and inactivation of eEF-2. eEF-2 contains a modified His residue known as diphthamide and it is this residue that is the target of the toxin. The process of moving a peptidyl-tRNA from the A-site to the P-site is termed translocation. Translocation is catalyzed by eEF-2 coupled to GTP hydrolysis. In the process of translocation the ribosome is moved along the mRNA such that the next codon of the mRNA resides under the A-site.

You Are a Visiting Physician Treating Patients at a Clinic