Diphtheria toxin

Function

Diphtheria toxin (DT) is a toxin which is secreted by the bacteria causing diphtheria. DT catalyzes the transfer of NAD to a diphthamide residue in the elongation factor-2 and thus inhibiting protein synthesis.^[1] See also Toxins.

Disease

A lethal dose of DT is ca. 0.1 μg per 1 kg of bodyweight.

Relevance

DT is used in several drugs as chemotherapeutic agent and as an immunotoxin.

Structural highlights

The biological assembly of Diphtheria toxin is dimer. DT is proteolitically cleaved into 2 fragments. Fragment A contains the catalytic domain (C) and fragment B contains the transmembrane (T) and receptor-binding (R) domains. DT active site is located in a cleft in the C domain.^[2] Water molecules are shown as red spheres. The 2 monomers of DT interact by domain swapping to form a compact, globular dimer structure.