| Name | Peptidase family C56 (PfpI endopeptidase family) |
|---|
| Family type peptidase | C56.001 - PfpI peptidase (Pyrococcus furiosus), MEROPS Accession MER0002455 (peptidase unit: 27-162) |
| Content of family | Peptidase family C56 contains the putative PfpI endopeptidase of Pyrococcus furiosus. |
| History |
Identifier created: MEROPS 5.4 (23 March 2001)
The discovery and characterisation of the PfpI endopeptidase (C56.001) have been reviewed by Hicks et al., 2004. |
| Catalytic type | Cysteine |
| Active site residues | E74 C100 H101 |
| Active site | Active site residues are proposed to be Cys100 and His101 in Pyrococcus furiosus PfpI endopeptidase (see the Alignment) (Du et al., 2000). It is evidently not possible for the side chains of these adjacent residues to interact to form a catalytic dyad in one polypeptide chain, but in the crystal, the enzyme forms a hexameric ring structure, and the active sites are proposed to be formed at the interfaces between three pairs of monomers. Functional catalytic dyads formed by residues from different subunits are not known from any other family of peptidases. Putative catalytic triads have been recognised in crystal structures: Cys/His/Glu in the yeast YDR533c protein (C56.004) (Graille et al., 2004) and Cys/His/Asp in Escherichia coli Hsp31 (C56.006) (Zhao et al., 2003). These have the geometry expected of catalytic triads similar to that of papain. |
| Activities and specificities | The only member of the family for which peptidase activity has been reported is the PfpI endopeptidase (C56.001). This shows a preference for bulky, hydrophobic P1 residues, and Suc-Ala-Ala-Phe-NHMec serves is a test substrate (Halio et al., 1997). The enzyme acts only on peptides of less than 20 amino acids (Hicks et al., 2004). It should be noted that the specificity for hydrophobic P1 residues is similar to that of peptidases in family S8, which are also expressed by Pyrococcus furiosus, so care is needed in distinguishing the two activities. |
| Inhibitors | An early study indicated that PfpI endopeptidase is inhibited by PMSF and DFP, and not by iodoacetate (Blumentals et al., 1990; Hicks et al., 2004). This was indicative of a serine peptidase rather than a cysteine peptidase, and further work is needed. |
| Molecular structure | The structure of PfpI endopeptidase (C56.001) was reported by Du et al. (2000), and structures are also available for the homologues yeast YDR533c protein (C56.004) (Graille et al., 2004) and Escherichia coli Hsp31 (C56.006) (Zhao et al., 2003). The proteins have the alpha/beta hydrolase fold, and are placed in subclan PC(C) because of their structural resemble to aspartyl dipeptidase (S51.001), the type peptidase of clan PC. |
| Clan | PC |
| Subclan | PC(C) |
| Basis of clan assignment | Protein fold of the peptidase unit for members of this family resembles aspartyl dipeptidase, the type example for clan PC. |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| PfpI peptidase | C56.001 | Yes |
| DJ-1 putative peptidase | C56.002 | Yes |
| Mername-AA100 putative peptidase | C56.003 | - |
| YDR533C putative peptidase | C56.004 | Yes |
| Hsp31 peptidase | C56.006 | Yes |
| Mername-AA101 non-peptidase homologue | C56.971 | - |
| phosphoribosylformylglycinamidine synthase | C56.972 | - |
| Mername-AA234 non-peptidase homologue | C56.973 | - |
| Mername-AA296 non-peptidase homologue | C56.974 | - |
| ES1 protein homolog, mitochondrial | C56.975 | Yes |
| protein deglycase 2 | C56.976 | Yes |
| At3g02720 (Arabidopsis thaliana) | C56.A01 | Yes |
| At3g54600 (Arabidopsis thaliana) | C56.A02 | - |
| chromosome XV reading frame ORF yor391c (Saccharomyces cerevisiae) | C56.A03 | Yes |
| protein SNO4 (Saccharomyces cerevisiae) | C56.A04 | Yes |
| SPCC757.03c (Schizosaccharomyces pombe) | C56.A05 | - |
| DDB_G0276405 (Dictyostelium discoideum) | C56.A06 | - |
| Family C56 non-peptidase homologues | non-peptidase homologue | Yes |
| Family C56 unassigned peptidases | unassigned | - |
