Family M24

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

M24A

Summary Holotypes Alignment Tree Genomes Literature

M24B

Summary Holotypes Alignment Tree Genomes Literature

Summary for family M24

Family type peptidaseM24.001 - methionyl aminopeptidase 1 (Escherichia-type) (Escherichia coli), MEROPS Accession MER0001243 (peptidase unit: 1-264)
Content of familyPeptidase family M24 contains exopeptidases that require co-catalytic ions of cobalt or manganese.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeMetallo
Active siteFamily 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 specificitiesFamily M24 contains exopeptidases with that are either aminopeptidases or dipeptidyl-peptidases. The methionyl aminopeptidases of subfamily M24A cleave the MetXaa (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.
InhibitorsFumagillin is an inhibitor of type II methionyl aminopeptidase (Sin et al., 1997). Apstatin is an inhibitor of aminopeptidase P (Prechel et al., 1997).
Molecular structureThe 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.
ClanMG
Basis of clan assignmentType family of clan MG.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsThe 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 relevanceFumagillin related angiogenesis inhibitors of type II methionyl aminopeptidase are of interest to the pharmaceutical industry for the treatment of solid tumours.
Statistics for family M24Sequences:14521
Identifiers:37
Identifiers with PDB entries:19
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M24A
Name Peptidase subfamily M24A
Subfamily type peptidase M24.001 - methionyl aminopeptidase 1 ({Escherichia}-type) (Escherichia coli), MEROPS Accession MER0001243 (peptidase unit: 1-264)
Active site residues H79 D97 D108 H171 E204 E235 
Statistics Sequences: 5995
Identifiers: 14
Identifiers with PDB entries: 6
Other databases CATH 3.90.230.10
HOMSTRAD Peptidase_M24
HSSP 1mat
INTERPRO IPR002467
PANTHER PTHR10804
PFAM PF00557
SCOP 55921
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)M24.001Yes
methionyl aminopeptidase 2M24.002Yes
methionyl aminopeptidase 1 (eukaryote)M24.017Yes
mitochondrial methionyl aminopeptidaseM24.028-
methionyl aminopeptidase (archaean-type) (Pyrococcus furiosus)M24.035Yes
methionyl aminopeptidase 1 (Staphylococcus-type)M24.036Yes
Mername-AA020 peptidase homologueM24.950-
Mername-AA226 peptidase homologue (Homo sapiens)M24.976-
At2g44180 (Arabidopsis thaliana)M24.A02-
At1g13270 (Arabidopsis thaliana)-type peptidaseM24.A05-
At4g37040 (Arabidopsis thaliana)-type peptidaseM24.A06-
At3g25740 (Arabidopsis thaliana)M24.A07-
CG5188 g.p. (Drosophila melanogaster)M24.A12-
MAL8P1.140 g.p. (Plasmodium falciparum)M24.A13-
subfamily M24A non-peptidase homologuesnon-peptidase homologue-
subfamily M24A unassigned peptidasesunassignedYes
Subfamily M24B
Name Peptidase subfamily M24B
Subfamily type peptidase M24.004 - aminopeptidase P (bacteria) (Escherichia coli), MEROPS Accession MER0001244 (peptidase unit: 172-433)
Active site residues H244 D261 D272 H351 H355 H362 E384 E407 
Statistics Sequences: 7646
Identifiers: 18
Identifiers with PDB entries: 11
Other databases CATH 3.90.230.10
HOMSTRAD hsd1az9
HSSP 1a16
INTERPRO IPR001131
PANTHER PTHR10804
PFAM PF00557
SCOP 55921
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Xaa-Pro dipeptidase (bacteria-type)M24.003Yes
aminopeptidase P (bacteria)M24.004Yes
aminopeptidase P2M24.005-
bacillus Xaa-Pro aminopeptidaseM24.006-
Xaa-Pro dipeptidase (eukaryote)M24.007Yes
hyperthermophile prolidaseM24.008Yes
aminopeptidase P1M24.009Yes
aminopeptidase P3M24.026-
leucine aminopeptidase (Thermotoga-type)M24.031Yes
Mername-AA273 peptidaseM24.032Yes
aminopeptidase P (Streptomyces-type)M24.033-
PH0974 dipeptidaseM24.034Yes
At4g36760 g.p. (Arabidopsis thaliana) and similarM24.037-
aminopeptidase P (Plasmodium falciparum-type)M24.038Yes
At3g05350 (Arabidopsis thaliana)-type peptidaseM24.A04-
YFR006W g.p. (Saccharomyces cerevisiae)M24.A09-
FRA1 g.p. (Saccharomyces cerevisiae)M24.A10-
SPBC4F6.19c g.p. (Schizosaccharomyces pombe)M24.A11Yes
subfamily M24B non-peptidase homologuesnon-peptidase homologueYes
subfamily M24B unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
proliferation-association protein 1M24.973Yes
FACT complex subunit SPT16M24.974-
proliferation-associated protein 1-like (Homo sapiens chromosome X)M24.975-
Mername-AA227 peptidase homologue (Homo sapiens)M24.977-
proliferation-associated protein 2G4M24.978-
family M24 non-peptidase homologuesnon-peptidase homologueYes
family M24 unassigned peptidasesunassigned-