Zheng W, Johnston S A, Joshua-Tor L
Center for Biomedical Inventions, Department of Medicine, University of Texas-Southwestern Medical Center, Dallas 75235-8573, USA.
Cell. 1998 Apr 3;93(1):103-9. doi: 10.1016/s0092-8674(00)81150-2.
The Gal6 protease is in a class of cysteine peptidases identified by their 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 clefts. 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 of the C terminus of Gal6 rather than the sequence of the substrate. We propose a model to explain these diverse activities and Gal6's singular ability to inactivate bleomycin.
