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ART Database

CLADE: EvpP (ARTC000004)

FAMILY: TNT (ARTF000078)

Description

A family comprising the ART domain of tuberculosis necrotizing toxin. It is present in bacteria and fungi. The core structure of the ART domain contains only 6 beta-strands (unlike all other known toxins that use NAD+ - in them there are 7 beta-strands).

InterPro - IPR025331

This is the C-terminal domain of CpnT secreted by Mycobacterium tuberculosis (Mtb). It induces necrosis of infected cells to evade immune responses. Mtb utilizes the protein CpnT to kill human macrophages by secreting its C-terminal domain (CTD), named tuberculosis necrotizing toxin (TNT), that induces necrosis. It acts as a NAD+ glycohydrolase which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol of infected macrophages resulting in necrotic cell death [PUBMED:26237511]. CpnT transports its toxic CTD from the cell surface of M. tuberculosis by proteolytic cleavage, where the toxin is cleaved to induce host cell death [PUBMED:24753609]. Structural analysis determined that the TNT core contains only six beta-strands as opposed to seven found in all known NAD+-utilizing toxins, and is significantly smaller, with only two short alpha-helices and two 3/10 helices. Furthermore, the putative NAD+ binding pocket identified Q822, Y765 and R757 as residues possibly involved in NAD+-binding and hydrolysis based on similar positions of catalytic amino acids of ADP-ribosylating toxins. Glutamine 822 residue was detected to be highly conserved among TNT homologues [PUBMED:26237511].

Sequences
Aligned domain sequences
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Unaligned domain sequences
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Full sequences
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Structures

Name Structure Additional informations
4QLP Download structure Reference structure
6YGE Download structure Reference structure
6YGF Download structure Reference structure
6YGG Download structure Reference structure
Literature
  • PMID: 26237511
  • PMID: 24753609
  • Origin

    Source: Pfam 34.0, rp75 Number of sequences: 775 Average length of the domain: 91 aa HMM: Model length: 90 Clustering level: 80% Alignment: ClustalO Additional information: sequences longer than 50 amino acids