PROSITE documentation PDOC52035 [for PROSITE entry PS52035]

Peptidase family M14 domain profile

Carboxypeptidases (CPs) hydrolyse peptide bonds in target proteins to release C-terminal amino acids. These enzymes have been classified into different families according to sequence similarity, mechanism and function. One of the largest groups, carrying a single catalytic Zn(2+) in the active site, is the M14 family. This is divided into four subfamilies known as M14A, M14B, M14C and M14D. In general, M14A and M14B carboxypeptidases either function within the secretory pathway or are themselves secreted. The members of the M14A subfamily are produced as pro-enzymes that are activated following the cleavage of N-terminal segments. The M14B subfamily are produced as active enzymes with a transthyretin-like domain at the C-terminus. The M14C group consists of bacterial enzymes related to γ-D-glutamyl-(L)-meso-diaminopimelate peptidase I and process components of the bacterial cell wall. Like their M14A relatives, they also carry an N-terminal extension. Members of the M14D subfamily are referred to as cytosolic carboxypeptidases (CCPs) to reflect their cellular location [1,2,3].

The M14 family metallocarboxypeptidase domain displays an α/β/α sandwich structure with a central mixed parallel-antiparallel β sheet flanked on both sides by several helices (see <PDB:2C1C>). The active site is located at the basis of a deep groove and consists of a distorted tetrahedral Zn(2+) coordination site (a pair of histidines, a glutamate, and a coordinated water molecule) surrounded by catalytic residues that stabilize intermediates during hydrolysis. A Glu residue polarizes the nucleophilic water and donates a hydrogen to the leaving amine [1,2,3].

The profile we developed covers the entire peptidase family M14 domain.