Peptidase_S11

• PFAM accession number: PF00768
• Interpro abstract (IPR001967):

  Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [ (PUBMED:7845208) ]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence [ (PUBMED:7845208) ]. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [ (PUBMED:7845208) ].

  Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [ (PUBMED:7845208) ]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [ (PUBMED:7845208) ]. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [ (PUBMED:7845208) (PUBMED:8439290) ].

  This group of serine peptidases belong to MEROPS peptidase family S11 (D-Ala-D-Ala carboxypeptidase A family, clan SE). The protein fold of the peptidase domain for members of this family resembles that of D-Ala-D-Ala-carboxypeptidase B, the type example for clan SE.

  Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [ (PUBMED:7845208) ]. They include a wide range of peptidase activity, including exopeptidase, endo-peptidase, oligopeptidase and omega-peptidase activity. Over 20 families (denoted S1 - S27) of serine protease have been identified, these being grouped into 6 clans (SA, SB, SC, SE, SF and SG) on the basis of structural similarity and other functional evidence. Structures are known for four of the clans (SA, SB, SC and SE): these appear to be totally unrelated, suggesting at least four evolutionary origins of serine peptidases and possibly many more [ (PUBMED:7845208) ].

  Not with standing their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C clans have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [ (PUBMED:7845208) ]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (SA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [ (PUBMED:7845208) (PUBMED:8439290) ].

  Bacterial cell walls are complex structures containing amino acids and amino sugars, with alternating chains of N-acetylglucosamine and N-acetyl-muramic acid units linked by short peptides [ (PUBMED:7845208) ]: the link peptide in Escherichia coli is L-alanyl-D-isoglutamyl-L-meso-diaminopimelyl-D-alanine. The chains are usually cross-linked between the carboxyl of D-alanine and the free amino group of diaminopimelate. During the synthesis of peptidoglycan, the precursor has the described tetramer sequence with an added C-terminal D-alanine [ (PUBMED:7845208) ].

  D-Ala-D-Ala carboxypeptidase A is involved in the metabolism of cell components [ (PUBMED:1741619) ]; it is synthesised with a leader peptide to target it to the cell membrane [ (PUBMED:7845208) ]. After cleavage of the leader peptide, the enzyme is retained in the membrane by a C-terminal anchor. There are three families of serine-type D-Ala-D-Ala peptidase, which are also known as low molecular weight penicillin-binding proteins.

  Family S11 contains only D-Ala-D-Ala peptidases, unlike families S12 and S13, which contain other enzymes, such as class C beta-lactamases and D-amino-peptidases [ (PUBMED:7845208) ]. Although these enzymes are serine proteases, some members of family S11 are partially inhibited by thiol-blocking agents [ (PUBMED:1930140) ].

• GO process: proteolysis (GO:0006508)
• GO function: serine-type D-Ala-D-Ala carboxypeptidase activity (GO:0009002)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry Peptidase_S11