ART Database

A family present in bacteria and viruses, it includes diphtheria toxin secreted by lysogenic strains of Corynebacterium diphtheriae.

Diphtheria toxin (EC) is a 58kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis [PUBMED:8573568]. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows: NAD + + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide. The crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution [PUBMED:1589020]. The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the alpha + beta type; a transmembrane (TM) domain, which consists of 9 alpha-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened beta-barrel with a jelly-roll-like topology [PUBMED:1589020]. The TM- and receptor binding-domains together constitute fragment B. This entry represents the N-terminal catalytic domain (also known as the C domain). This domain has an unusual beta+alpha fold [PUBMED:9012663]. The C domain blocks protein synthesis by transfer of ADP-ribose from NAD to a diphthamide residue of EF-2 [PUBMED:7833808, PUBMED:8573568].

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Source: Pfam 34.0, rp75 Number of sequences: 6 Average length of the domain: 127 aa HMM: Model length: 147 Clustering level: 80% Alignment: ClustalO Additional information: sequences longer than 50 amino acids