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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Aminopeptidases / chemistry
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Aminopeptidases / metabolism*
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Binding Sites
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Carboxypeptidases / chemistry
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Carboxypeptidases / metabolism*
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Cloning, Molecular
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Crystallography, X-Ray
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Cysteine Endopeptidases / chemistry*
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Cysteine Endopeptidases / metabolism*
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DNA Primers
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Escherichia coli
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Kinetics
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Leupeptins / pharmacology
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Peptide Synthases / chemistry
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Peptide Synthases / metabolism*
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Point Mutation
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Protein Conformation*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Deletion
Substances
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DNA Primers
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Leupeptins
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Macromolecular Substances
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Recombinant Proteins
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Carboxypeptidases
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Aminopeptidases
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Cysteine Endopeptidases
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bleomycin hydrolase
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Peptide Synthases
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leupeptin
Associated data
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PDB/1A6R
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PDB/1GCB
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PDB/3GCB