| Family type peptidase | M10.001 - matrix metallopeptidase-1 (Homo sapiens), MEROPS Accession MER0001063 (peptidase unit: 98-276) |
| Content of family | Peptidase family M10 contains metalloendopeptidases. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
|
| Catalytic type | Metallo |
| Active site | The zinc ligands and catalytic glutamate of family M10 occur in the motif HEXXHXXGXXH, as in families M12, M43 and M57. |
| Activities and specificities | Like other peptidases in subclan MA(M), the peptidases of family M10 are synthesized as inactive precursors. However, differences exist in the mechanisms of activation. The inactivity of the proenzymes of the matrixins in subfamily M10A is due to what is known as a "cysteine switch" (Van Wart & Birkedal-Hansen, 1990). In this, there is an interaction between a conserved cysteine in the propeptide and the catalytic zinc in the ion that prevents the binding of a crucial water molecule. Because of the importance of cysteine in the latency of the proenzymes, they can commonly be activated by thiol-blocking agents such as aminophenylmecuric acetate (APMA). Serralysin, and activation of the proenzyme is by removal of an N-terminal propeptide. |
| Inhibitors | Like other metallopeptidases, the peptidases in family M10 are inhibited by chelating agents, and many potent inhibitors such as batimastat have been synthesized as possible drugs. The timp proteins in family I35 inhibit the peptidases of subfamily M10A, but not M10B. Serralysin is inhibited by a 10kDa inhibitor from Serratia (I38.003). |
| Molecular structure | The peptidases of family M10 belong to a group of peptidases known as the "metzincins", due to a conserved methionine C-terminal to the zinc ligands which forms what is known as a "Met-turn" (Bode et al., 1993). Both subfamilies of M10 contain mosaic proteins. Serralysin contains a glycine-rich C-terminal domain Gly-Gly-Xaa-Gly-Asn-Asp which has a role in binding calcium ions. The matrixins possess at least one C-terminal domain homologous to hemopexin and vitronectin, thought to help the enzyme bind to the extracellular matrix. The gelatinases have acquired three domains homologous to type II segments of fibronectin nested within the peptidases unit. |
| Clan | MA |
| Subclan | MA(M) |
| 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 | The matrixins in family M10 are mostly secreted proteins that function extracellularly. The matrixins in subfamily M10A are synthesized with conventional signal peptides, but the bacterial serralysin in subfamily M10B is synthesized without a signal peptide, and is secreted by a different mechanism. The matrixins play important roles in the degradation of connective tissue matrix proteins and both in normal tissue turnover and in pathological tissue damage. |
| Pharmaceutical and biotech relevance | The matrixins in family M10 are drug targets for prevention of pathological tissue damage an tumour invasion (Heath & Grochow, 2000). |
| Statistics for family M10 | Sequences: | 12952 |
| Identifiers: | 65 |
| Identifiers with PDB entries: | 21 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| matrix metallopeptidase-1 | M10.001 | Yes |
| matrix metallopeptidase-8 | M10.002 | Yes |
| matrix metallopeptidase-2 | M10.003 | Yes |
| matrix metallopeptidase-9 | M10.004 | Yes |
| matrix metallopeptidase-3 | M10.005 | Yes |
| matrix metallopeptidase-10 (Homo sapiens-type) | M10.006 | Yes |
| matrix metallopeptidase-11 | M10.007 | Yes |
| matrix metallopeptidase-7 | M10.008 | Yes |
| matrix metallopeptidase-12 | M10.009 | Yes |
| envelysin | M10.010 | - |
| matrix metallopeptidase-10 (rodent type) | M10.011 | - |
| GM1-MMP (Glycine max) | M10.012 | - |
| matrix metallopeptidase-13 | M10.013 | Yes |
| membrane-type matrix metallopeptidase-1 | M10.014 | Yes |
| membrane-type matrix metallopeptidase-2 | M10.015 | - |
| membrane-type matrix metallopeptidase-3 | M10.016 | Yes |
| membrane-type matrix metallopeptidase-4 | M10.017 | - |
| matrix metallopeptidase-18 | M10.018 | - |
| matrix metallopeptidase-20 | M10.019 | Yes |
| matrix metallopeptidase-19 | M10.021 | - |
| matrix metallopeptidase-23B | M10.022 | Yes |
| membrane-type matrix metallopeptidase-5 | M10.023 | - |
| membrane-type matrix metallopeptidase-6 | M10.024 | - |
| HMMP (Hydra vulgaris)-like peptidase | M10.025 | - |
| matrix metallopeptidase-21 | M10.026 | - |
| matrix metallopeptidase-22 | M10.027 | - |
| matrix metallopeptidase-26 | M10.029 | - |
| matrix metallopeptidase-28 | M10.030 | - |
| Dm1 matrix metallopeptidase | M10.031 | - |
| matrixin V | M10.032 | - |
| collagenase-like A peptidase (rodent) | M10.033 | - |
| collagenase-like B peptidase (rodent) | M10.034 | - |
| Dm2-matrix metallopeptidase | M10.036 | - |
| matrix metallopeptidase-23A | M10.037 | - |
| At5-MMP (Arabidopsis thaliana) | M10.038 | - |
| Cydia pomonella granulovirus metallopeptidase | M10.040 | - |
| Pta1 peptidase | M10.065 | - |
| karilysin | M10.066 | Yes |
| Zmp-1 peptidase (Caenorhabditis-type) | M10.067 | - |
| Zmp-2 peptidase (Caenorhabditis sp.) | M10.068 | - |
| macrophage elastase homologue (chromosome 8, Homo sapiens) | M10.950 | - |
| Mername-AA156 protein | M10.971 | - |
| matrix metallopeptidase-like 1 | M10.973 | - |
| similar to matrix metallopeptidase 25 (Rattus norvegicus) | M10.974 | - |
| At2-MMP (Arabidopsis thaliana) | M10.A01 | - |
| At4-MMP (Arabidopsis thaliana) | M10.A02 | - |
| At1-MMP (Arabidopsis thaliana) | M10.A04 | - |
| At3-MMP (Arabidopsis thaliana) | M10.A05 | - |
| Mername-AA284 peptidase | M10.A06 | - |
| Zmp-3 (Caenorhabditis elegans) | M10.A07 | - |
| Zmp-4 (Caenorhabditis elegans) | M10.A08 | - |
| Zmp-5 (Caenorhabditis elegans) | M10.A09 | - |
| Zmp-6 (Caenorhabditis elegans) | M10.A10 | - |
| Subfamily M10A non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M10A unassigned peptidases | unassigned | - |
