THE UNUSUAL ACTIVE-SITE OF GAL6 BLEOMYCIN HYDROLASE CAN ACT AS A CARBOXYPEPTIDASE, AMINOPEPTIDASE, AND PEPTIDE LIGASE/

The Gal6 protease is in a class of cysteine peptidases identified by t heir ability to inactivate the anti-cancer drug bleomycin. The protein forms a barrel structure with the active sites embedded in a channel as in the proteasome. In Gal6 the C termini lie in the active site cle fts. We show that Gal6 acts as a carboxypeptidase on its C terminus to convert itself to an aminopeptidase and peptide ligase. The substrate specificity of the peptidase activity is determined by the position o f the C terminus of Gal6 rather than the sequence of the substrate. We propose a model to explain these diverse activities and Gal6's singul ar ability to inactivate bleomycin.