Catlytic type: Aspartate; residues with large hydrophobic sidechains on either side of the scissile bond, but several members have more restricted specificities that allow protein-processing functions (see additional Info); The amino acid sequences show signal peptides and propeptides except for bacterial homologues which also lack disulfide bridges and are probably cytoplasmic (Rawlings & Bateman, 2009). Many three-dimensional structures have been described. The catalytic site is located between the two lobes of the molecules, and a 'flap' structure containing a conserved Tyr residue controls specificity (James, 2004; Hong & Tang, 2004). Several of the peptidases are glycosylated (e.g. cathepsin D, A01.009) and a few are membrane-bound (memapsin-1 and memapsin-2, A01.041 and A01.004, respectively). Some family A1 peptidases from plants (e.g. phytepsin, A01.020) contain inserted saposin-like sequences, and the effects of these on enzymatic activity have been investigated (Payie et al., 2003). The secreted proteins in subfamily A usually have three conserved disulfide bridges, whereas in subfamily B there are six, and the unusual stability of nepenthesin (A01.040) to a wide pH range has been attributed to these disulfide bridges (Takahashi et al., 2005).
Endopeptidases (most of which are most active at acidic pH)