Summary for clan AE
| Clan type peptidase | A25.001 - gpr peptidase (Bacillus megaterium), MEROPS Accession MER0001292 (peptidase unit: 17-371); PDB accession 1C8B_A |
| History | MEROPS 5.61 (29 October 2001) |
| Description | Water nucleophile; water bound by two Asp |
| Contents of clan | Peptidase clan AE contains families A25 (of HybD peptidase) and A31 (of gpr peptidase). |
| Evidence | The homology of families A25 and A31 is shown by similarities in the protein folds of gpr peptidase (A25.001) and HybD peptidase (A31.001). There are also limited similarities between the sequences in the two families, as described by Pei & Grishin (2002)) (see the Alignment). Three residues that seem to be equivalent are highly conserved in both families: Asp (sometimes Glu in A31), Asp, and a basic residue (Lys in A25 and His in A31) (see the family and clan Alignments). The basic residue is apparently not an active site residue, because replacement or deletion of Lys224 had no effect on the activity of the gpr peptidase (Carroll & Setlow, 2005). |
| Catalytic mechanism | The catalytic mechanism is not understood, but the residues that are essential for activity in both families are a pair of aspartates (one of which is sometimes replaced by glutamate in A31). This justifies regarding these as atypical aspartic peptidases (Carroll & Setlow, 2005). The earlier view that these may be metallopeptidases (Pei & Grishin, 2002) is not consistent with the fact that the isolated peptidases in both families contain no metal ions, and are not inhibited by chelating agents. The hydrogenase substrates of the peptidases in family A31 contain nickel, but the peptidases do not bind nickel (Theodoratou et al., 2000), and MEROPS suggests that the role of the nickel is in substrate recognition, not catalysis. |
| Peptidase activity | The peptidases in both families are endopeptidases, and those in family A25 also undergo autolytic activation reactions (Carroll & Setlow, 2005). However, there are few similarities in substrate specificities between the two families (Pei & Grishin, 2002). |
| Protein fold | Crystal structures have been determined for members of both families in the clan (HybD peptidase, Fritsche et al., 1999; gpr peptidase, Ponnuraj etal, 2000), but only for the precursor of the gpr peptidase. Peptidases in the clan are alpha/beta proteins with a core of a three-layered sandwich, alpha-beta-alpha. The beta sheet is five-stranded with the strands (in the order 21354) and strand 4 is antiparallel to the others. Peptidases in family A25 have an additional N-terminal alpha/beta subdomain. |
| Activation mechanism | Peptidases in family A25 auto-activate by cleavage of an N-terminal peptide (Illades-Aguiar & Setlow, 1994; Carroll & Setlow, 2005), but there is no evidence of proenzymes in family A31. |
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Other databases
| PFAM | CL0095 |
|
| SCOP | 53163 |
Families
| A25 |
gpr peptidase (Bacillus megaterium) |
Yes |
| A31 |
HybD peptidase (Escherichia coli) |
Yes |
Distribution of clan AE among Kingdoms of Organisms
| A25 | - | - | - | - | - | - | - |
| A31 | - | - | - | - | - | - | - |
| Clan | - | - | - | - | - | - | - |
