Peptidase M20, glutamate carboxypeptidase (IPR017150)

Short name: Pept_M20_glutamate_carboxypep

Overlapping homologous superfamilies

Family relationships

  • Peptidase M20 (IPR002933)
    • Peptidase M20, glutamate carboxypeptidase (IPR017150)


Glutamate carboxypeptidase (also known as carboxypeptidase G2, CPDG2, CPG2 or folate hydrolase G2) belongs to the peptidase M20 family. It is a periplasmic enzyme that is synthesized with a signal peptide. CPDG2 is a dimeric zinc-dependent exopeptidase, with two domains, a catalytic domain, which provides the ligands for the two zinc ions in the active site, and a dimerization domain [PMID: 9083113]. CPDG2 cleaves the C-terminal glutamate moiety from a wide range of N-acyl groups, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl, and pteroyl groups to release benzoic acid, phenol, and aniline mustards. It is used clinically to treat methotrexate toxicity by hydrolyzing it to inactive and non-toxic metabolites. It is also proposed for use in antibody-directed enzyme prodrug therapy; for example, glutamate can be cleaved from glutamated benzoyl nitrogen mustards, producing nitrogen mustards with effective cytotoxicity against tumor cells [PMID: 15668713, PMID: 10090777, PMID: 11912146].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.