Family C80

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family C80

Family type peptidaseC80.001 - RTX self-cleaving toxin (Vibrio cholerae), MEROPS Accession MER0031601 (peptidase unit: 3447-3639)
Content of familyPeptidase family C80 contains self-cleaving proteins that are precursors of bacterial toxins.
History Identifier created: MEROPS 8.2 (4 August 2008)
Family C80 contains bacterial toxins that self-process by a cysteine peptidase mechanism. These include Vibrio cholera RTX toxin (C80.001), and Clostridium difficile toxins A (C80.002) and B (C80.003). Some pathogenic bacteria produce unrelated toxins that also require activation and processing, the processing often being autolytic as it is in anthrax lethal factor (M34.001), tentoxilysin (the tetanus neurotoxin, M27.001) and bontoxilysin (the botulinum neurotoxin, M27.002), all of which are metallopeptidases.
Catalytic typeCysteine
Active site residuesH3532 C3581 
Active siteSite-directed mutagenesis has been used to identify functional residues (Asp, His, Cys) in Clostridium toxin B (Egerer et al., 2007) and (His, Cys) in cholera RTX toxin (Sheahan et al., 2007) (see Alignment).
Activities and specificitiesBoth the cholera RTX and Clostridium toxin B have a preference for Leu in P1. Peptidase activity is not restricted to self-cleavage and the processed RTX toxin has been shown to be able to degrade the leucine-rich protein YopM (Prochazkova et al., 2009).
InhibitorsAutolysis is prevented by standard cysteine peptidase inhibitors such as N-ethylmaleimide or iodoacetamide (Egerer et al., 2007). Inhibition by pepstatin and EPNP has been reported, which led to the suggestion that a host pepsin homologue processed the Clostridium toxins (Pfeifer et al., 2003) or that the toxins are themselves aspartic peptidases (Reineke et al., 2007).
Molecular structureThe tertiary structure of the cholera RTX toxin has been solved (Lupardus et al., 2008) and shows a structure similar to that of caspase-1. Family C80 is therefore included in clan CD.
ClanCD
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functionsThe cholera RTX toxin is effectively a polyprotein, and processing to release the individual domains is required. The self-processing (stimulated by GTP) has been shown to release the actin-crosslinking domain, and possibly also the Rho-inactivation domain and other domains (Sheahan et al., 2007). The cholera toxin causes actin crosslinking which leads to depolymerization and rounding of cells (Sheahan et al., 2007). Each Clostridium toxin contain a glucosyltransferase domain which has to be released and translocated to the cytoplasm of the target cells where Rho GTPases are modified (Egerer et al., 2007).
Statistics for family C80Sequences:101
Identifiers:3
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
RTX self-cleaving toxinC80.001Yes
self-cleaving toxin A (Clostridium-type)C80.002-
self-cleaving toxin B (Clostridium-type)C80.003Yes
family C80 non-peptidase homologuesnon-peptidase homologue-
family C80 unassigned peptidasesunassigned-