Cathepsin Z (also known as Cathepsin X , and MEROPS identifier C01.013) is predominantly a cysteine-type carboxypeptidase with limited endopeptidase or dipeptidyl-peptidase activity, mainly against synthetic substrates [, ]. The substrate specificity has been examined by peptide scanning and shows that proline is not tolerated in the P1 or P1' positions and poorly accepted in P2, and Tyr, Met and Cys are marginally prefered in P2, P1 and P1' [, ].Cathepsin X is synthesized as an inactive zymogen, but the propeptide lacks the ERFNIN motif characteristic of lysosomal cysteine peptidases. A disulfide bridge can be formed between the proregion and the enzyme which leads to inactivation of the zymogen by the formation of a reversible covalent bond with the active site residue []. From the crystal structure of the mature enzyme, a short, five-residue 'mini-loop' which includes the motif His-Xaa-Xaa-Xaa-Tyr restricts access to the S2' binding pocket, and it is the histidine that confers carboxypeptidase activity []. Rotation of the histidine ring permits dipeptidyl-peptidase substrates to bind. The presence of an exposed RGD motif allows binding to beta3-integrin []and the enzyme may have a role in cell signalling. Cathepsin X deficiency leads to accelerated cell senescence []. Cathepsin X also regulates the immune response to Helicobacter pylori infection [, ].
