Family M66


Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family M66

Family type peptidaseM66.001 - StcE peptidase (Escherichia coli), MEROPS Accession MER0020010 (peptidase unit: 249-550)
Content of familyPeptidase family M66 contains a single metallopeptidase.
History Identifier created: MEROPS 6.4 (24 September 2003)
Peptidase StcE is a virulence factor found in Shiga toxigenic Escherichia coli organisms.
Catalytic typeMetallo
Active site residuesH446 E447 H450 H456 
Active siteThe active site residues of StcE peptidase (M66.001) are located in an HEXXH motif. The third metal ligand is located six residues C-terminal to the motif. Mutation of the catalytic Glu to Asp prevents both cleavage and binding of C1 esterase inhibitor (I04.024) (Lathem et al., 2002).
Activities and specificitiesIt has been demonstrated that StcE peptidase will only cleave C1 esterase inhibitor (Lathem et al., 2002). This cleavage occurs within the heavily glycosylated N-terminal region of C1 esterase inhibitor and is different to that of elastase (Lathem et al., 2004).
Molecular structureStcE peptidase contains a N-terminal signal peptide (Lathem et al., 2002). Members of M66 do not have a conserved methionine (known as a "Met-turn") C-terminal to the active site motif, but are assigned to clan MA(M) on the basis of their HEXXHXXGXXH motif.
Basis of clan assignmentPredicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH
Distribution of family Bacteria details  
Archaea -  
Protozoa details  
Fungi details  
Plants details  
Animals -  
Viruses -  
Biological functionsStcE is encoded by a gene on a large virulence plasmid called pO157 that is carried by E. coli strain O157:H7. The protein is secreted via the etp type II secretion system, which is located downstream of StcE and is positively regulated by Ler (Lathem et al., 2002). It is thought that StcE is part of the global virulence regulon central to pathogenicity and it has been suggested that StcE may protect the bacterium and the host cell from complement-mediated lysis and potentially damaging inflammatory events (Lathem et al. (2004)). These organisms are known to cause conditions such as diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome.
Pharmaceutical and biotech relevanceThe peptidase C1 esterase inhibitor is an important regulator of the classical and alternative complement cascades, intrinsic coagulation and contact inactivation. Disruption of these systems by Shiga toxigenic E. coli may cause life-threatening disease. StcE could be a target for the treatment of these infections.
Statistics for family M66Sequences:186
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
StcE peptidaseM66.001Yes
family M66 non-peptidase homologuesnon-peptidase homologue-
family M66 unassigned peptidasesunassigned-