title: The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase.
abstract: 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.
authors.affiliation: Center for Biomedical Inventions, Department of Medicine, University of Texas-Southwestern Medical Center, Dallas 75235-8573, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: S A
authors.initials: SA
authors.lastname: Johnston
authors.forename: L
authors.initials: L
authors.lastname: Joshua-Tor
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D017931:DNA Primers; D004926:Escherichia coli; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism*; D017354:Point Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D007976:Leupeptins; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D002268:Carboxypeptidases; D000626:Aminopeptidases; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; D010453:Peptide Synthases; C032854:leupeptin