Family M26

Family

Summary Holotypes Alignment Tree Genomes Literature

Summary for family M26

Family type peptidaseM26.001 - IgA1-specific metallopeptidase (Streptococcus sanguinis), MEROPS Accession MER0001173 (peptidase unit: 530-1878)
Content of familyPeptidase family M26 contains endopeptidases.
History Identifier created: Methods Enzymol. 248:183-228 (1995)
Some pathogenic bacteria synthesise endopeptidases that cleave the "hinge" region of the heavy chain of immunoglobulin A (IgA) (Plaut, A. G.2004). These include serine peptidases in family S6 and metallopeptidases in families M26 and M64. Many of these enzymes are highly selective for IgA as substrate, and it seems reasonable to presume that their action is somehow beneficial to the bacteria, but exactly how is not known with certainty (Kilian et al., 1996).
Catalytic typeMetallo
Active site residuesH1494 E1495 H1498 
Active siteCatalytic residues are two histidine residues (metal ligands) and a glutamate (catalytic) in the HEXXH motif (see the Alignment). Activity was lost when the HEMTH motif in M26.001 was mutated to FKMTH (Gilbert et al., 1991). The third ligand of zinc is probably one of the highly-conserved Glu residues C-terminal to the HEXXH motif.
Activities and specificitiesThe peptidases of family M26 cleave the heavy chain of human IgA1 at the Pro227Thr228 bond, and no other substrates are known (Plaut, 2004). Monomeric and polymeric, serum and secreted forms of IgA1 are cleaved, but human IgA2 has a sequence deletion in the hinge region that makes it resistant to the action of the IgA peptidases. The cleavage in the hinge region of IgA1 releases intact, functional Fc and Fab fragments of the immunoglobulin.
Molecular structureNo crystal structure is available, and the limits of the peptidase unit cannot be defined with any confidence. Most of the peptidases are synthesised as single-chain proteins of about 200 kDa (about 1670 residues, typically including no cysteine). The C-terminal part of the molecule contains about 10 tandem repeats of a sequence of 18 - 20 residues (VXPXQVXXXPEYXGXXXGAX). There is no clear evidence of post-translational processing of the protein.
ClanMA
SubclanMA(E)
Basis of clan assignmentActive site residues for members of this family and family M4 occur in the motif HEXXH
Distribution of family Bacteria details  
Archaea details  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functionsThe IgA peptidases of family M26 are tightly associated with the bacterial cell surface (in contrast to some of those in family S6, which are secreted in soluble form). The possible significance of the IgA peptidases to bacterial infection has been reviewed (Kilian et al., 1996).
Statistics for family M26Sequences:289
Identifiers:4
Identifiers with PDB entries:0
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
IgA1-specific metallopeptidaseM26.001-
ZmpB metallopeptidase (Streptococcus sp)M26.002-
ZmpC metallopeptidaseM26.003-
IgA1 peptidase (Streptococcus suis)M26.004-
family M26 non-peptidase homologuesnon-peptidase homologue-
family M26 unassigned peptidasesunassigned-