The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase

Zheng, W., Johnston, S. A., Joshua-Tor, L. (1998) The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase. Cell, 93 (1). pp. 103-9. ISSN 0092-8674 (Print)0092-8674 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9546396
DOI: 10.1016/S0092-8674(00)81150-2

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.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Aminopeptidases chemistry metabolism Binding Sites Carboxypeptidases chemistry metabolism Cloning, Molecular Crystallography X-Ray Cysteine Endopeptidases chemistry metabolism DNA Primers Escherichia coli Kinetics Leupeptins pharmacology Macromolecular Substances Models Molecular Molecular Sequence Data Mutagenesis, Site-Directed Peptide Synthases chemistry metabolism Point Mutation Protein Conformation Recombinant Proteins chemistry metabolism Sequence Deletion
Subjects: Investigative techniques and equipment > X-Ray Diffraction
diseases & disorders > cancer > drugs and therapies
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein structure rendering
Investigative techniques and equipment > x ray crystallography
CSHL Authors:
Communities: CSHL labs > Joshua-Tor lab
Depositing User: CSHL Librarian
Date Deposited: 20 Mar 2012 20:47
Last Modified: 06 Sep 2017 14:17
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Dataset ID:
URI: http://repository.cshl.edu/id/eprint/25500

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