| Name | Peptidase family P1 (DmpA aminopeptidase family) |
|---|
| Family type peptidase | P01.001 - DmpA aminopeptidase (Ochrobactrum anthropi), MEROPS Accession MER0004893 (peptidase unit: 250-375) |
| Content of family | Peptidase family P1 contains aminopeptidases and self-processing proteins. |
| History |
Identifier created: MEROPS 9.8 (17 December 2012)
The DmpA aminopeptidase (P01.001) is an enzyme of the bacterium Ochrobactrum anthropi that was discovered because of its hydrolysis of D-Ala NHPhNO2 (Fanuel et al., 1999). The DmpA aminopeptidase self-activates to produce a two-chain form in which the new N-terminus is the serine that is the nucleophile in the self-cleaving reaction. The ThnT protein from Streptomyces cattleya (P01.101), which is involved in the biosynthesis of the beta-lactam antibiotic thienamycin, also activates itself but cleavage results in an N-terminal threonine (Buller et al., 2012). Family P1 is thus the only family in which the residue bearing the nucleophile is not strictly conserved in an active peptidase. Because the nucleophile can be either serine or threonine, the family is named P1. |
| Catalytic type | Mixed (C, S, T) catalytic type |
| Active site residues | T,S250 |
| Active site | The DmpA peptidase is an N-terminal nucleophile hydrolase with a serine nucleophile (see the Alignment) that is generated by an autolytic cleavage (Fanuel et al., 1999). The tertiary structure of the ThnT protein (P01.101), which autoactivates, shows that the N-terminal nucleophile in the processed form is threonine (Buller et al., 2012). |
| Activities and specificities | Despite its hydrolysis of D-AlaNHPhNO2, DmpA shows specificity for release of amino acid residues in the L-configuration in its action on peptides. This change in stereospecificity according to whether the substrate is a simple amino acid amide or ester, or a peptide, is a distinctive feature of the activity of the enzyme (Frere & Van Beeumen, 2004). Mature ThnT is an amidase that hydrolyses a pantetheinyl moiety and its only peptidase activity is self-activation (Buller et al., 2012). Commonly, self-cleaving proteins express no further proteolytic activity, though some of the mature components of the proteasome (##XT01.001##) and the DmpA aminopeptidase are exceptions. |
| Inhibitors | DmpA was not affected by antipain, bestatin, chymostatin, leupeptin, Pefabloc SC, EDTA or 1,10-phenanthroline (Frere & Van Beeumen, 2004). |
| Molecular structure | The structure of DmpA shows a homotetramer in which each monomer contains two non-covalently-associated polypeptide chains (Bompard-Gilles et al., 2000). The 375-residue precursor protein is activated by elimination of an N-terminal Met residue, and then cleavage of the bond -Gly249Ser- that exposes the N-terminal nucleophile. However, it was pointed out by Bompard-Gilles et al. (2000) and further stressed by Cheng & Grishin (2005) that the fold of DmpA differs in connectivity and directionality of strands from those of the previously-known N-terminal nucleophile hydrolases that MEROPS places in clan PB. Cheng & Grishin (2005) proposed the term 'DOM fold' for DmpA and its homologues, and MEROPS places peptidase family P1 alone in clan PE. |
| Clan | PE |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles that of archaean proteasome subunit B, the type example of clan PB. |
