C1 Peptidase family (MEROPS database nomenclature), also referred to as the papain family; composed of two subfamilies of cysteine peptidases (CPs), C1A (papain) and C1B (bleomycin hydrolase). Papain-like enzymes are mostly endopeptidases with some exceptions like cathepsins B, C, H and X, which are exopeptidases. Papain-like CPs have different functions in various organisms. Plant CPs are used to mobilize storage proteins in seeds while mammalian CPs are primarily lysosomal enzymes responsible for protein degradation in the lysosome. Papain-like CPs are synthesized as inactive proenzymes with N-terminal propeptide regions, which are removed upon activation. Bleomycin hydrolase (BH) is a CP that detoxifies bleomycin by hydrolysis of an amide group. It acts as a carboxypeptidase on its C-terminus to convert itself into an aminopeptidase and peptide ligase. BH is found in all tissues in mammals as well as in many other eukaryotes. It forms a hexameric ring barrel structure with the active sites imbedded in the central channel. Some members of the C1 family are proteins classified as non-peptidase homologs which lack peptidase activity or have missing active site residues.
Comment:The catalytic residues of C1 family peptidases are Cys and His, forming a catalytic dyad. Two other residues play an important role in catalysis: a Gln preceding the catalytic Cys, believed to help in the formation of the oxyanion hole; and an Asn residue which orients the imidazolium ring of the catalytic His.
Comment:The active sites of bleomycin hydrolase are imbedded in a channel, as in the proteasome, within a hexameric ring barrel structure. They are accessible only by substrates through the central channel.
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