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Diphtheria toxin

Diphtheria toxin, C domain
PDB 1xdt EBI.jpg
complex of diphtheria toxin and heparin-binding epidermal growth factor
Identifiers
Symbol Diphtheria_C
Pfam PF02763
Pfam clan CL0084
InterPro IPR022406
SCOP 1ddt
SUPERFAMILY 1ddt
TCDB 1.C.7
Diphtheria toxin, T domain
PDB 1xdt EBI.jpg
complex of diphtheria toxin and heparin-binding epidermal growth factor
Identifiers
Symbol Diphtheria_T
Pfam PF02764
InterPro IPR022405
SCOP 1ddt
SUPERFAMILY 1ddt
TCDB 1.C.7
Diphtheria toxin, R domain
PDB 1xdt EBI.jpg
complex of diphtheria toxin and heparin-binding epidermal growth factor
Identifiers
Symbol Diphtheria_R
Pfam PF01324
InterPro IPR022404
SCOP 1ddt
SUPERFAMILY 1ddt
TCDB 1.C.7
tox diphtheria toxin precursor
Identifiers
Organism Corynebacterium diphtheriae
Symbol tox
Entrez 2650491
RefSeq (Prot) NP_938615
UniProt Q6NK15
Other data
EC number 2.4.2.36
Chromosome genome: 0.19 - 0.19 Mb

Diphtheria toxin is an exotoxin secreted by Corynebacterium diphtheriae, the pathogenic bacterium that causes diphtheria. Unusually, the toxin gene is encoded by a bacteriophage (a virus that infects bacteria). The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis.

Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two subunits linked by disulfide bridges, known as an A-B toxin. Binding to the cell surface of the B subunit (the less stable of the two subunits) allows the A subunit (the more stable part of the protein) to penetrate the host cell.

The crystal structure of the diphtheria toxin homodimer has been determined to 2.5 Ångstrom resolution. The structure reveals a Y-shaped molecule consisting of three domains. Fragment A contains the catalytic C domain, and fragment B consists of the T and R domains:

The diphtheria toxin has the same mechanism of action as the enzyme NAD(+)—diphthamide ADP-ribosyltransferase (EC 2.4.2.36). It catalyzes the transfer of NAD+ to a diphthamide residue in eEF-2, inactivating this protein. It does so by ADP-ribosylating the unusual amino acid diphthamide. In this way, it acts as a RNA translational inhibitor. The catalysed reaction is as follows:


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