Structures and evolution

Abstract The lysosomal cysteine peptidases considered here belong to the papain family of peptidases, termed family Cl by Rawlings and Barrett [1187]. (At the time of writing, it is just emerging that legumain, an endopeptidase specific for the hydrolysis of asparaginyl bonds, is probably an additional lysosomal cysteine proteinase, of a separate family, C13 [1783]. It is too early to say much more about this, at this time.) Among the amino acid sequences known for the papain family, numbering more than 250, are those of enzymes from bacteria, fungi, protozoa and plants, as well as animals. Most of the proteins in the family are endopeptidases, but there are also some exopeptidases and proteins without known catalytic activity. The available amino acid sequences of vertebrate lysosomal cysteine peptidases (Table 19) provide a basis for dividing them into three groups, as is illustrated by a dendrogram for the human enzymes in Fig. 14 (below). One group contains enzymes that are closest in structure to papain: cathepsins H, K, L and S, whereas cathepsin B and dipeptidyl peptidase I represent separate groups, remote from the cathepsin L set and from each other.