Family M3
Summary for family M3
| Family type peptidase | M03.001 - thimet oligopeptidase (Rattus norvegicus), MEROPS Accession MER0001149 (peptidase unit: 2-687) |
| Content of family | Peptidase family M3 contains metallopeptidases with varied activities. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
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| Catalytic type | Metallo |
| Active site | Like all peptidases in subclan MA(E), the peptidases in family M3 contain the HEXXH motif that forms the active site in conjunction with a C-terminally-located Glu residue. A single zinc ion is ligated by the sidechains of the two His residues, and the more C-terminal Glu. |
| Activities and specificities | Varied peptidase reactions are catalysed by members of family M3. The commonest is a form of endopeptidase activity that is restricted to substrates of low molecule mass, and is therefore termed 'oligopeptidase'. Both thimet oligopeptidase (M03.001) and neurolysin (M03.002) are oligopeptidases, acting only on substrates of less than about 19 amino acid residues, with a particular preference for cleaving near the C-terminus (Knight et al., 1995). The bacterial peptidyl-dipeptidase Dcp (M03.005) liberates C-terminal dipeptides, but the most unusual form of peptidase activity in the family is that of the mitochondrial intermediate peptidase (M03.006) that cleaves N-terminal octapeptides from proteins during their import into mitochondria (Isaya & Kalousek, 1995). |
| Inhibitors | No protein inhibitors of peptidases in this family have been described. Some oligopeptides are inhibitory, and many potent small-molecule inhibitors have been synthesised (e.g. Vincent et al., 1997 ). |
| Molecular structure | The peptidases of family M3 are high-molecular-mass (about 80 kDa) zinc metalloendopeptidases. The molecular structure of neurolysin (M03.002) described by Brown et al., (2001) shows that large structural elements prevent the access of substrates to the active site except through a deep narrow channel. This doubtless accounts for the oligopeptidase specificity. The structure of neurolysin shows similarities to those of peptidyl-dipeptidase A peptidase unit 2 (M02.004) and carboxypeptidase Pfu (M32.002) (Natesh et al., 2003), in other families of subclan MA(E). |
| Clan | MA |
| Subclan | MA(E) |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of thermolysin, the type example for clan MA. |
| Biological functions | Most of the peptidases are synthesised without signal peptides or propeptides, and function intracellularly. Mitochondrial intermediate peptidase is an exception, having a typical mitochondrial leader peptide. One likely function of peptidases in family M3 is the intracellular degradation of oligopeptides. These could include cleaved signal peptides, and products of protein degradation. In vertebrate organisms, some of these peptides might otherwise be bound by MHC class I (York et al., 2003). Many mammalian, biologically-active peptides are excellent substrates for the oligopeptidase actions of thimet oligopeptidase and neurolysin, and some authors have proposed important roles for the enzymes in the catabolism of such peptides. In support of this, evidence has been offered that the predominantly intracellular enzymes are to some extent membrane-bound or secreted. |
| Statistics for family M3 | Sequences: | 16702 |
| Identifiers: | 18 |
| Identifiers with PDB entries: | 8 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
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Peptidases not assigned to subfamily
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| Peptidases and Homologues |
MEROPS ID |
Structure |
| Family M3 unassigned peptidases | unassigned | - |
