Family M20

Family

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

M20A

Summary Holotypes Alignment Tree Genomes Literature

M20B

Summary Holotypes Alignment Tree Genomes Literature

M20C

Summary Holotypes Alignment Tree Genomes Literature

M20D

Summary Holotypes Alignment Tree Genomes Literature

M20F

Summary Holotypes Alignment Tree Genomes Literature

Summary for family M20

Family type peptidaseM20.001 - glutamate carboxypeptidase (Pseudomonas sp.), MEROPS Accession MER0001266 (peptidase unit: 23-415)
Content of familyPeptidase family M20 contains exopeptidases: carboxypeptidases, dipeptidases and a specialised aminopeptidase.
History Identifier created: Biochem.J. 290:205-218 (1993)
Catalytic typeMetallo
Active siteThe 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 specificitiesAmongst 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.
InhibitorsAs 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 structureCrystal 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.
ClanMH
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of Vibrio aminopeptidase, the type example for clan MH.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsIn 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 relevanceGlutamate 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 M20Sequences:38060
Identifiers:44
Identifiers with PDB entries:18
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily M20A
Name Peptidase subfamily M20A
Subfamily type peptidase M20.001 - glutamate carboxypeptidase (Pseudomonas sp.), MEROPS Accession MER0001266 (peptidase unit: 23-415)
Active site residues H112 D114 D141 E175 E176 D,E200 H385 
Statistics Sequences: 9204
Identifiers: 16
Identifiers with PDB entries: 6
Other databases CATH 3.40.630.10
HOMSTRAD apbact
HSSP 1cg2
INTERPRO IPR002933
PANTHER PTHR11014
PFAM PF01546
SCOP 53204
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
glutamate carboxypeptidaseM20.001Yes
Gly-Xaa carboxypeptidaseM20.002-
peptidase VM20.004Yes
DapE peptidaseM20.010Yes
carboxypeptidase PM20D1M20.011-
BT3549 putative peptidaseM20.016Yes
aminoacylaseM20.973Yes
acetyl-lysine deacetylaseM20.975-
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 homologuesnon-peptidase homologue-
subfamily M20A unassigned peptidasesunassignedYes
Subfamily M20B
Name Peptidase subfamily M20B
Subfamily type peptidase M20.003 - peptidase T (Escherichia coli), MEROPS Accession MER0001421 (peptidase unit: 13-408)
Active site residues H78 D80 D140 E173 E174 D196 H379 
Statistics Sequences: 3395
Identifiers: 2
Identifiers with PDB entries: 3
Other databases CATH 3.40.630.10
HOMSTRAD hs1fnoa
INTERPRO IPR002933
PFAM PF01546
SCOP 53204
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
peptidase TM20.003Yes
BC4143 proteinM20.018Yes
subfamily M20B non-peptidase homologuesnon-peptidase homologue-
subfamily M20B unassigned peptidasesunassignedYes
Subfamily M20C
Name Peptidase subfamily M20C
Subfamily type peptidase M20.007 - Xaa-His dipeptidase (Escherichia coli), MEROPS Accession MER0001283 (peptidase unit: 2-485)
Active site residues H76 D78 D115 E145 E146 D169 H457 
Statistics Sequences: 2279
Identifiers: 2
Identifiers with PDB entries: 1
Other databases INTERPRO IPR002933
PANTHER PTHR11014
PFAM PF01546
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Xaa-His dipeptidaseM20.007Yes
Pep581 peptidaseM20.012-
subfamily M20C non-peptidase homologuesnon-peptidase homologue-
subfamily M20C unassigned peptidasesunassigned-
Subfamily M20D
Name Peptidase subfamily M20D
Subfamily type peptidase M20.008 - carboxypeptidase Ss1 (Sulfolobus solfataricus), MEROPS Accession MER0002007 (peptidase unit: 1-393)
Active site residues C,D,E81 D83 D,H109 E141 E,H142 H168 H365 
Statistics Sequences: 16990
Identifiers: 14
Identifiers with PDB entries: 3
Other databases INTERPRO IPR002933
PANTHER PTHR11014
PFAM PF01546
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
carboxypeptidase Ss1M20.008-
Mername-AA028 peptidaseM20.009-
indoleacetyl amino acid hydrolaseM20.014Yes
YxeP putative peptidaseM20.015Yes
HMRA peptidase (Staphylococcus-type)M20.019Yes
p-aminobenzoyl-glutamate hydrolase subunit AM20.020-
cytosolic beta-alanyl-lysine dipeptidaseM20.021-
At1g51780 (Arabidopsis thaliana)M20.A01-
At3g02875 (Arabidopsis thaliana)-type peptidaseM20.A02-
At5g56650 (Arabidopsis thaliana)M20.A03-
At1g51760 (Arabidopsis thaliana)-type peptidaseM20.A04-
At1g44350 (Arabidopsis thaliana)-type peptidaseM20.A05-
At5g54140 (Arabidopsis thaliana)M20.A06-
amhX g.p. (Bacillus subtilis)M20.A26-
ykuR g.p. (Bacillus subtilis)M20.A27-
subfamily M20D non-peptidase homologuesnon-peptidase homologue-
family M20D unassigned peptidasesunassigned-
Subfamily M20F
Name Peptidase subfamily M20F
Subfamily type peptidase M20.005 - carnosine dipeptidase II (Mus musculus), MEROPS Accession MER0026494 (peptidase unit: 1-475)
Active site residues H99 D101 D132 E166 E167 D195 H445 
Statistics Sequences: 5203
Identifiers: 6
Identifiers with PDB entries: 3
Other databases INTERPRO IPR002933
PANTHER PTHR11014
PFAM PF01546
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
carnosine dipeptidase IIM20.005Yes
carnosine dipeptidase IM20.006Yes
Xaa-methyl-His dipeptidaseM20.013-
Dug1 peptidaseM20.017Yes
pes-9 g.p. (Caenorhabditis elegans)M20.A14-
Y71H2AM.11 g.p. (Caenorhabditis elegans)M20.A15-
subfamily M20F non-peptidase homologuesnon-peptidase homologue-
subfamily M20F unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
allantoate amidohydrolaseM20.976Yes
At4g20070 (Arabidopsis thaliana)M20.A07-
DDB_G0279291 g.p. (Dictyostelium discoideum)M20.A18-
rocB g.p. (Bacillus subtilis)M20.A20-
family M20 non-peptidase homologuesnon-peptidase homologueYes
family M20 unassigned peptidasesunassigned-