| Family type peptidase | M01.001 - aminopeptidase N (Homo sapiens), MEROPS Accession MER0000997 (peptidase unit: 301-517) |
| Content of family | Peptidase family M1 contains mainly aminopeptidases. |
| History |
Identifier created: Biochem.J. 290:205-218 (1993)
|
| Catalytic type | Metallo |
| Active site residues | H388 E389 H392 E411 Y477 |
| Active site | A catalytic zinc ion bound is by two histidines and a glutamate. The histidines are within an "HEXXH" motif on one long helix with the glutamate on another antiparallel helix. The catalytic mechanism is believed to involve activation of a water molecule by the zinc ion. The glutamate of the HEXXH motif is known to be important for catalysis and a tyrosine may also be involved. |
| Activities and specificities | The peptidases of family M1 are dependent on a single zinc ion for activity, and all members of the family act on the N-terminus of polypeptides, many of them being aminopeptidases. The family also contains pyroglutamyl-peptidase II (M01.008), an omega peptidase that releases pyroglutamate from thyrotropin-releasing hormone. Cleavage of dipeptides also occurs and aminopeptidase N was formerly known as Cys-Gly dipeptidase. Although the aminopeptidases show a preference for some amino acids, each is capable of releasing a variety of residues, so names like 'alanyl aminopeptidase' can be misleading. We are not aware of any member of family M1 that hydrolyses Xaa-Pro-bonds, and some that are normally aminopeptidases release the Xaa-Pro dipeptide. Leukotriene A4 hydrolase (M01.004) has an additional catalytic activity as an epoxide hydrolase converting leukotriene A4 to the inflammatory mediator leukotriene B4, which is dependent on a second active site (Mueller et al., 1996). |
| Inhibitors | Bestatin and amastatin are effective inhibitors, as are metal chelators such as EDTA and 1,10-phenanthroline, but these agents inhibit other metallo-aminopeptidases and indeed other metallopeptidases also. There are no known protein inhibitors. Cytosolic alanyl aminopeptidase (M01.010) is inhibited by puromycin. |
| Molecular structure | The structure of leukotriene A4 hydrolase (Thunnissen et al., 2001) shows a three-domain protein in which the catalytic domain is the middle one. The catalytic domain contains an antiparallel beta sheet and alpha helices, similar to that of thermolysin (M04.001), so family M1 is included in clan MA. |
| 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. |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| aminopeptidase N | M01.001 | Yes |
| lysyl aminopeptidase (bacteria) | M01.002 | - |
| aminopeptidase A | M01.003 | Yes |
| leukotriene A4 hydrolase | M01.004 | Yes |
| alanyl aminopeptidase (bacterial-type) | M01.005 | Yes |
| Ape2 aminopeptidase | M01.006 | - |
| Aap1' aminopeptidase | M01.007 | - |
| pyroglutamyl-peptidase II | M01.008 | - |
| aminopeptidase N (actinomycete-type) | M01.009 | - |
| cytosol alanyl aminopeptidase | M01.010 | - |
| cystinyl aminopeptidase | M01.011 | Yes |
| aminopeptidase G | M01.012 | - |
| aminopeptidase N (insect) | M01.013 | - |
| aminopeptidase B | M01.014 | - |
| aminopeptidase H11 (nematode) | M01.015 | - |
| aminopeptidase Ey | M01.016 | - |
| TMA108 protein (Saccharomyces cerevisiae) | M01.017 | - |
| endoplasmic reticulum aminopeptidase 1 | M01.018 | Yes |
| tricorn interacting factor F2 | M01.020 | - |
| tricorn interacting factor F3 | M01.021 | Yes |
| arginyl aminopeptidase-like 1 | M01.022 | - |
| ERAP2 aminopeptidase | M01.024 | Yes |
| aminopeptidase-1 (Caenorhabditis-type) | M01.025 | - |
| aminopeptidase Q | M01.026 | - |
| aminopeptidase O | M01.028 | - |
| M1 aminopeptidase (Plasmodium spp.) | M01.029 | Yes |
| aminopeptidase N2 (insect) | M01.030 | - |
| cold-active aminopeptidase (Colwellia psychrerythraea)-type peptidase | M01.031 | Yes |
| lysyl aminopeptidase 1 (Streptomyces sp.) | M01.032 | - |
| lysyl endopeptidase (Streptomyces albulus) | M01.033 | - |
| leukotriene A4 hydrolase (Saccharomyces cerevisiae) | M01.034 | Yes |
| LePepA g.p. (Legionella pneumophila) | M01.035 | Yes |
| Tata binding protein associated factor | M01.972 | Yes |
| similar to RIKEN cDNA 4833403I15 (Rattus norvegicus) | M01.973 | - |
| slamdance (Drosophila melanogaster) | M01.A02 | - |
| BG:DS00365.1 g.p. (Drosophila melanogaster) | M01.A03 | - |
| CG5845 g.p. (Drosophila melanogaster) | M01.A05 | - |
| CG5849 g.p. (Drosophila melanogaster) | M01.A06 | - |
| CG3502 g.p. (Drosophila melanogaster) | M01.A07 | - |
| CG11951 g.p. (Drosophila melanogaster) | M01.A08 | - |
| CG11956 g.p. (Drosophila melanogaster) | M01.A09 | - |
| Dgri protein (Drosophila melanogaster) | M01.A10 | - |
| CG8774 g.p. (Drosophila melanogaster) | M01.A11 | - |
| CG8773 g.p. (Drosophila melanogaster) | M01.A12 | - |
| CG31343 g.p. (Drosophila melanogaster) | M01.A13 | - |
| CG5839 g.p. (Drosophila melanogaster) | M01.A14 | - |
| Y105E8A.a g.p. (obs.) (Caenorhabditis elegans) | M01.A15 | - |
| Y67D8C.9 g.p. (Caenorhabditis elegans) | M01.A16 | - |
| T16G12.1 g.p. (Caenorhabditis elegans) | M01.A17 | - |
| ZC416.6 g.p. (Caenorhabditis elegans) | M01.A18 | - |
| R03G8.4 g.p. (Caenorhabditis elegans) | M01.A19 | - |
| T12E12.6 g.p. (Caenorhabditis elegans) | M01.A20 | - |
| T16G12.1 g.p. (Caenorhabditis elegans) | M01.A21 | - |
| Y42A5A.1 g.p. (Caenorhabditis elegans) | M01.A22 | - |
| R03G8.6 g.p. (Caenorhabditis elegans) | M01.A23 | - |
| CG1009 g.p. (Drosophila melanogaster) | M01.A24 | - |
| At4g33090 g.p. (Arabidopsis thaliana) | M01.A25 | - |
| At5g13520 g.p. (Arabidopsis thaliana) | M01.A26 | - |
| CG10602 g.p. (Drosophila melanogaster) | M01.A27 | - |
| pam-1 g.p. (Caenorhabditis elegans) | M01.A28 | - |
| ape1 g.p. (Schizosaccharomyces pombe) | M01.A29 | - |
| DDB_G0273539 g.p. (Dictyostelium discoideum) | M01.A30 | - |
| PsaA g.p. (Dictyostelium discoideum) | M01.A31 | - |
| lkhA g.p. (Dictyostelium discoideum) | M01.A32 | - |
| PF2063 g.p. (Pyrococcus furiosus) | M01.A33 | - |
| Family M01 non-peptidase homologues | non-peptidase homologue | - |
| Family M01 unassigned peptidases | unassigned | Yes |
