Family M43
Summary for family M43
| Name | Peptidase family M43 (cytophagalysin family) |
| Family type peptidase | M43.001 - cytophagalysin (Cytophaga sp.), MEROPS Accession MER0002084 (peptidase unit: 67-282) |
| Content of family | Peptidase family M43 contains metallo-endopeptidases. |
| History |
Identifier created: Handbook of Proteolytic Enzyme, Academic Press, London (1998)
|
| Catalytic type | Metallo |
| Active site | Family M43 members contain three zinc binding histidines and a catalytic glutamate in an HEXXHXXGXXH motif. There are two subfamilies, and the sequences of peptidases in subfamily M43B contain a conserved methionine (C-terminal to the HEXXHXXGXXH motif) found in other members of clan MA(M). |
| Activities and specificities | Cytophagalysin (M43.001) cleaves beta-casein at Pro63 Gly64 and Met102 Ala103. Both pappalysin-1 (M43.004) and papplysin-2 (M43.005) can cleave insulin-like growth factor binding-protein 5 (IGFBP-5) at Ser143 Lys144 (Laursen et al., 2001). Pappalysin-1 can cleave IGFBP-1 at Met135 Lys136 and also IGFBP-4. Boldt et al. (2001) also showed that pappalysin-1 can cleave itself at Phe386 Asn387, causing a loss of peptidase activity. |
| Activities and specificities | Cytophagalysin (M43.001) cleaves beta-casein at Pro63 Gly64 and Met102 Ala103. Both pappalysin-1 (M43.004) and papplysin-2 (M43.005) can cleave insulin-like growth factor binding-protein 5 (IGFBP-5) at Ser143 Lys144 (Laursen et al., 2001). Pappalysin-1 can cleave IGFBP-1 at Met135 Lys136 and also IGFBP-4. Boldt et al. (2001) also showed that pappalysin-1 can cleave itself at Phe386 Asn387, causing a loss of peptidase activity. |
| Inhibitors | Cytophagalysin is inhibited by the metal chelator EDTA at millimolar concentrations Kamio & Sasagawa, 2004. Pappalysin-1 is also inhibited by metal chelating agents, including EDTA and 1,10-phenanthroline. |
| Molecular structure | Pappalysin is secreted as a 400-kDa dimer. The majority of sequences in family M43 (in subfamily B) show a conserved Met residue C-terminal to the zinc-binding motif that presumably indicates the presence of a "Met-turn" analogous to that in astacin (M12.001), the type peptidase of subclan M of clan MA. |
| Clan | MA |
| Subclan | MA(M) |
| Basis of clan assignment | Predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH |
|
Peptidases not assigned to subfamily
|
| Peptidases and Homologues |
MEROPS ID |
Structure |
| Family M43 unassigned peptidases | unassigned | - |