Target intelligence / Profile preview

Diphtheria toxin A-subunit (DTA)

Target
DTA
Molecular classification
Enzyme (ADP-ribosyltransferase), Bacterial toxin subunit, Catalytic protein, Fragment of A-B exotoxin
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Overview

The diphtheria toxin A-subunit (DTA) is the catalytic component of the diphtheria toxin produced by Corynebacterium diphtheriae and related species. DTA is responsible for the toxin’s action: after entering the host cell, it catalyzes the ADP-ribosylation of eukaryotic elongation factor 2 (EF-2), effectively halting protein synthesis and inducing cell death. The subunit alone cannot enter cells but is highly cytotoxic once inside. In clinical and research settings, DTA is used both as a tool for cell ablation and as a moiety in experimental targeted therapies, most notably in fusion proteins used for cancer treatment. The A-subunit is a validated therapeutic target in infectious disease (diphtheria) and oncology, where its potent cell death-inducing properties can be directed against unwanted cell populations. It poses substantial safety risks due to its extreme potency and potential for non-specific toxicity in systemic exposure.

Other names
DTAFragment ADiphtheria toxin catalytic subunitDiphtheria toxin A chain
02

Mechanism of action

Neutralization of toxin activity (antitoxins bind and inhibit) Preventing entry into host cells (by blocking receptor binding domain in engineered fusion proteins, thereby preventing DTA delivery) For immunotoxins, targeted delivery of DTA to specific cell types leads to EF-2 inactivation and cell death

03

Biological functions

Protein synthesis inhibition (by ADP-ribosylation of eukaryotic elongation factor 2, EF-2/eEF-2)Inducer of cell death/apoptosis (cytotoxic)Inhibition of cell proliferationMechanism for bacterial pathogenesis (causative agent of diphtheria)
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Disease associations

Infection (central to diphtheria pathology)Used in experimental models for cancer cell ablation
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Safety considerations

High cytotoxicity (a single molecule can kill a cell)Off-target toxicity in immunotoxin therapiesSystemic toxicity if not restricted to target cellsImmunogenicity (potential for immune response against bacterial protein)
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Interacting drugs

Diphtheria antitoxin (antibody therapy against A and B subunits; not a classic small-molecule drug but directly interacts)

2 more in the full profile.

07

Biomarkers

Presence of tox gene (diagnostic for Corynebacterium diphtheriae strains capable of producing toxin)Circulating diphtheria toxin (in infection; can be monitored for efficacy of antitoxin therapy)Susceptibility of cells to DTA-mediated EF-2 inhibition (used in research for selection)

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