249 – Carboxypeptidase Z

Publisher Summary This chapter describes the activity, specificity and structural chemistry of carboxypeptidase Z (CPZ). CPZ is a single-chain protein of approximately 71 kDa. Different splice variants have been detected, with the major form of human CPZ 641 amino acids in length. The crystal structure of CPZ has not been determined, but predictions of the structure have been made based on amino acid sequence similarities to other proteins. As with all members of the metallocarboxypeptidase family, CPZ contains a 300 residue domain that has approximately 20%–50% amino acid sequence identity with other family members. Following this, carboxypeptidase domain is an 80 residue region that has 40–50% amino acid sequence identity with the corresponding region of metallocarboxypeptidase D; this region of metallocarboxypeptidase D has been found to fold into a β sheet-rich structure that has homology with transthyretin. Based on the amino acid sequence similarity between CPZ and this region of metallocarboxypeptidase D, it is likely that the corresponding domain on CPZ also folds into a transthyretin-like domain.Upstream of the carboxypeptidase domain is a 120 residue Cys-rich region that has approximately 20%–30% amino acid sequence identity with a Cys-rich domain present in a number of proteins that bind Wnts.