Family M20
Summary for family M20
| Family type peptidase | M20.001 - glutamate carboxypeptidase (Pseudomonas sp.), MEROPS Accession MER0001266 (peptidase unit: 23-415) |
| Content of family | Peptidase family M20 contains exopeptidases: carboxypeptidases, dipeptidases and a specialised aminopeptidase. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
|
| Catalytic type | Metallo |
| Active site | The peptidases are of the "co-catalytic" type, binding two metal ions per monomer of protein. There are five metal-ligand residues, because one ligates both metal ions, and the general arrangement of these is: His/Asp, Asp, Glu, Glu/Asp, His. With the addition of two catalytic residues (bold), the full set of active site residues becomes: His/Asp, Asp, Asp, Glu, Glu, Glu/Asp, His, but there are variations in the individual subfamilies that can be seen in their Alignments. The roles of the two catalytic zinc ions can be described as stabilization of the tetrahedral intermediate and activation of the catalytic water molecule (Jozic et al., 2002). |
| Activities and specificities | Amongst the varied peptidases in family M20 are carboxypeptidase such as the glutamate carboxypeptidase from Pseudomonas (M20.001), the thermostable carboxypeptidase Ss1 of broad specificity from the archaea such as Sulfolobus sp. (M20.008) and the yeast Gly-X carboxypeptidase (M20.002). The dipeptidases include bacterial dipeptidase, peptidase V (M20.004), a eukaryotic, non-specific dipeptidase (M20.005), and two Xaa-His dipeptidases (carnosinases) (M20.006 and M20.007). There is also the bacterial aminopeptidase, peptidase T (M20.003) that acts only on tripeptide substrates and has therefore been termed a tripeptidase. |
| Inhibitors | As is expected for metallopeptidases, inhibition by EDTA and 1,10-phenanthroline are general. Nonspecific dipeptidase is potently inhibited by bestatin (Teufel et al., 2003). Peptidase V has the phosphinic inhibitor AspPsi[PO(2)CH(2)]AlaOH (Jozic et al., 2002). M20.001 is inhibited by phosphonothioic acid derivatives (Lu & Berkman, 2001), thiocarbamates (Khan et al., 1999) and phosphonamidothionate derivatives of glutamic acid (Rodriguez et al., 1999). |
| Molecular structure | Crystal structures are available for peptidases from subfamilies M20A and M20B, and they show protein folds typical of clan MH. Glutamate carboxypeptidase exists as a homodimer, and the structure shows that each monomer consists of two domains, of which the N-terminal is catalytic and the C-terminal links the monomers in the dimer. |
| Clan | MH |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of Vibrio aminopeptidase, the type example for clan MH. |
| Biological functions | In general, the peptidases hydrolyse the late products of protein degradation so as to complete the conversion of proteins to free amino acids. The Pseudomonas glutamate carboxypeptidase is a periplasmic enzyme that is synthesised with a signal peptide. Gly-X carboxypeptidase is a yeast enzyme that has a vacuolar localisation, and is synthesised with an N-terminal propeptide. In the cytosolic fractions of mammalian cells there are the non-specific dipeptidase and carnosinase. |
| Pharmaceutical and biotech relevance | Glutamate carboxypeptidase hydrolyses such folate analogues as methotrexate, and can be used to treat methotrexate toxicity (Krause et al., 2002). It is also proposed for use in antibody-directed enzyme prodrug therapy (ADEPT) (Khan et al., 1999). |
| Statistics for family M20 | Sequences: | 47025 |
| Identifiers: | 48 |
| Identifiers with PDB entries: | 22 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| glutamate carboxypeptidase | M20.001 | Yes |
| Gly-Xaa carboxypeptidase | M20.002 | - |
| peptidase V | M20.004 | Yes |
| DapE peptidase | M20.010 | - |
| carboxypeptidase PM20D1 | M20.011 | - |
| BT3549 putative peptidase | M20.016 | Yes |
| LysK isopeptidase (Thermus thermophilus) | M20.022 | Yes |
| aminoacylase | M20.973 | Yes |
| acetylornithine deacetylase ArgE | M20.974 | - |
| acetyl-lysine deacetylase | M20.975 | - |
| YgeY protein (Escherichia coli) | M20.A08 | - |
| C44E12.1 g.p. (Caenorhabditis elegans) | M20.A16 | - |
| ylmB g.p. (Bacillus subtilis) | M20.A19 | - |
| yodQ g.p. (Bacillus subtilis) | M20.A21 | - |
| BSn5_04310 g.p. (Bacillus subtilis) | M20.A22 | - |
| Bsubs1_010100013116 g.p. (Bacillus subtilis) | M20.A23 | - |
| PF1185 g.p. (Pyrococcus furiosus) | M20.A24 | - |
| PFC_08320 g.p. (Pyrococcus furiosus) | M20.A25 | - |
| Subfamily M20A non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M20A unassigned peptidases | unassigned | Yes |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| carboxypeptidase Ss1 | M20.008 | - |
| Mername-AA028 peptidase | M20.009 | - |
| indoleacetyl amino acid hydrolase | M20.014 | Yes |
| YxeP putative peptidase | M20.015 | Yes |
| HMRA peptidase (Staphylococcus-type) | M20.019 | Yes |
| p-aminobenzoyl-glutamate hydrolase subunit A | M20.020 | Yes |
| cytosolic beta-alanyl-lysine dipeptidase | M20.021 | - |
| At1g51780 (Arabidopsis thaliana) | M20.A01 | - |
| At3g02875 (Arabidopsis thaliana)-type peptidase | M20.A02 | - |
| At5g56650 (Arabidopsis thaliana) | M20.A03 | - |
| At1g51760 (Arabidopsis thaliana)-type peptidase | M20.A04 | - |
| At1g44350 (Arabidopsis thaliana)-type peptidase | M20.A05 | - |
| At5g54140 (Arabidopsis thaliana) | M20.A06 | - |
| amhX g.p. (Bacillus subtilis) | M20.A26 | - |
| ykuR g.p. (Bacillus subtilis) | M20.A27 | - |
| Subfamily M20D non-peptidase homologues | non-peptidase homologue | - |
| Subfamily M20D unassigned peptidases | unassigned | Yes |
|
Peptidases not assigned to subfamily
|
| Peptidases and Homologues |
MEROPS ID |
Structure |
| allantoate amidohydrolase | M20.976 | Yes |
| At4g20070 (Arabidopsis thaliana) | M20.A07 | - |
| DDB_G0279291 g.p. (Dictyostelium discoideum) | M20.A18 | Yes |
| rocB g.p. (Bacillus subtilis) | M20.A20 | - |
| Family M20 non-peptidase homologues | non-peptidase homologue | Yes |
| Family M20 unassigned peptidases | unassigned | Yes |
