Family M24
Summary for family M24
| Family type peptidase | M24.001 - methionyl aminopeptidase 1 (Escherichia-type) (Escherichia coli), MEROPS Accession MER0001243 (peptidase unit: 1-264) |
| Content of family | Peptidase family M24 contains exopeptidases that require co-catalytic ions of cobalt or manganese. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
|
| Catalytic type | Metallo |
| Active site | Family M24 is one of a number of metallopeptidase families that are described as being co-catalytic. In methionyl aminopeptidase (M24.001) from Escherischia coli, the two cobalt ions are bound by Asp108, His171 and Glu204, and Asp97, Asp108 and Glu204. The metal ligands are pentahedrally coordinated by Glu204. There is a catalytic His at position 79. In bacterial X-Pro aminopeptidase (M24.003) the metal ions are manganese rather than cobalt. |
| Activities and specificities | Family M24 contains exopeptidases with that are either aminopeptidases or dipeptidyl-peptidases. The methionyl aminopeptidases of subfamily M24A cleave the Met Xaa (where Xaa is any amino acid) bond in the removal of the initiating N-terminal methionine from newly synthesized proteins. The peptidases of subfamily M24B cleave the bond XaaPro. |
| Inhibitors | Fumagillin is an inhibitor of type II methionyl aminopeptidase (Sin et al., 1997). Apstatin is an inhibitor of aminopeptidase P (Prechel et al., 1997). |
| Molecular structure | The peptidases of the two subfamilies of M24 are grouped together on the basis of a common 'pitta-bread' fold (Bazan et al., 1994) similar to that of Pseudomonas putida creatinase. The fold contains both alpha helices and an anti-parallel beta sheet within two structurally similar domains that are thought to be derived from an ancient gene duplication. The active site is located between the two domains. The eukaryotic methionyl aminopeptidases of subfamily M24A contain an N-terminal extension that is not found in prokaryotic species. In the eukaryotic methionyl aminopeptidase I this N-terminal extension contains putative zinc finger consensus sequences. |
| Clan | MG |
| Basis of clan assignment | Type family of clan MG. |
| Biological functions | The methionyl aminopeptidases of subfamily M24A are essential for the removal of the initiating methionine of many proteins, acting co-translationally in association with the ribosomes (Chang et al., 1992). The X-Pro dipeptidase found in eukaryotes has a role in the cleavage of XaaPro linkages found in dipeptides associated with collagen recycling. Deficiency results in an increase of these dipeptides to toxic levels (Myara et al., 1994). |
| Pharmaceutical and biotech relevance | Fumagillin related angiogenesis inhibitors of type II methionyl aminopeptidase are of interest to the pharmaceutical industry for the treatment of solid tumours. |
| Statistics for family M24 | Sequences: | 23276 |
| Identifiers: | 40 |
| Identifiers with PDB entries: | 25 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| methionyl aminopeptidase 1 (Escherichia-type) | M24.001 | Yes |
| methionyl aminopeptidase 2 | M24.002 | Yes |
| methionyl aminopeptidase 1 (eukaryote) | M24.017 | Yes |
| mitochondrial methionyl aminopeptidase | M24.028 | - |
| methionyl aminopeptidase (archaean-type) (Pyrococcus furiosus) | M24.035 | Yes |
| methionyl aminopeptidase 1 (Staphylococcus-type) | M24.036 | Yes |
| Mername-AA020 peptidase homologue | M24.950 | - |
| Mername-AA226 peptidase homologue (Homo sapiens) | M24.976 | - |
| At2g44180 (Arabidopsis thaliana) | M24.A02 | - |
| At1g13270 (Arabidopsis thaliana)-type peptidase | M24.A05 | - |
| At4g37040 (Arabidopsis thaliana)-type peptidase | M24.A06 | Yes |
| At3g25740 (Arabidopsis thaliana) | M24.A07 | - |
| CG5188 g.p. (Drosophila melanogaster) | M24.A12 | - |
| MAL8P1.140 g.p. (Plasmodium falciparum) | M24.A13 | - |
| LCP55 (Arabidopsis thaliana) | M24.A14 | - |
| Subfamily M24A non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M24A unassigned peptidases | unassigned | Yes |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| Xaa-Pro dipeptidase (bacteria-type) | M24.003 | Yes |
| aminopeptidase P (bacteria) | M24.004 | Yes |
| aminopeptidase P2 | M24.005 | - |
| bacillus Xaa-Pro aminopeptidase | M24.006 | Yes |
| Xaa-Pro dipeptidase (eukaryote-type) | M24.007 | Yes |
| hyperthermophile prolidase | M24.008 | Yes |
| aminopeptidase P1 | M24.009 | Yes |
| aminopeptidase P3 | M24.026 | Yes |
| leucine aminopeptidase (Thermotoga-type) | M24.031 | Yes |
| Mername-AA273 peptidase | M24.032 | Yes |
| aminopeptidase P (Streptomyces-type) | M24.033 | - |
| PH0974 dipeptidase | M24.034 | Yes |
| At4g36760 g.p. (Arabidopsis thaliana) and similar | M24.037 | - |
| aminopeptidase P (Plasmodium falciparum-type) | M24.038 | Yes |
| metallopeptidase TvMP50 (Trichomonas vaginalis) | M24.040 | - |
| At3g05350 (Arabidopsis thaliana)-type peptidase | M24.A04 | - |
| YFR006W g.p. (Saccharomyces cerevisiae) | M24.A09 | - |
| FRA1 g.p. (Saccharomyces cerevisiae) | M24.A10 | - |
| SPBC4F6.19c g.p. (Schizosaccharomyces pombe) | M24.A11 | - |
| Subfamily M24B non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M24B unassigned peptidases | unassigned | Yes |
|
Peptidases not assigned to subfamily
|
| Peptidases and Homologues |
MEROPS ID |
Structure |
| YdpF (Escherischia coli) | M24.039 | Yes |
| proliferation-association protein 1 | M24.973 | Yes |
| FACT complex subunit SPT16 | M24.974 | Yes |
| proliferation-associated protein 1-like (Homo sapiens chromosome X) | M24.975 | - |
| Mername-AA227 peptidase homologue (Homo sapiens) | M24.977 | - |
| proliferation-associated protein 2G4 | M24.978 | Yes |
| Family M24 non-peptidase homologues | non-peptidase homologue | Yes |
| Family M24 unassigned peptidases | unassigned | Yes |
