Molecular and Structural Biology of Bleomycin and Its Resistance Determinants
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概要
- 論文の詳細を見る
An anti-tumor antibiotic, bleomycin (Bm), causes cell death as a result of multiple strand scissions by direct interaction with bacterial and tumor cell DNAs. Some prokaryotic and eukaryotic cells have a system to protect themselves from Bm-induced toxicity. In eukaryotes, the response of normal and tumor cells to toxicity depends on the level of Bm hydrolase activity. The inactivation system of Bm, which hydrolyzes the amide in the β-aminoalanine moiety of Bm, is also found in a few bacteria. We have shown that a Bm-resistance determinant, expressed in Bm-producing Streptomyces verticillus, the transposon Tn5 and methicillin-resistant Staphylococcus aureus, is a Bm-binding protein. A Bm N-acetylating enzyme, produced by S. verticillus, is also a Bm-resistance determinant. We have determined the X-ray crystal structures of Bm-binding proteins from S. verticillus and Tn5, designated BLMA and BLMT, respectively. Both crystal structures show that two Bm molecules bind to two Bm-binding pockets formed by the alternate arm exchange of two monomeric BLMA (BLMT) molecules. The Bm-binding proteins, complexed with Bm, are successfully crystallized and their X-ray crystal structures have been determined at high resolutions. The crystallographic analysis of the complexed protein gives a mode for binding to Bm: this is the first report regarding the X-ray crystal structure of the Bm molecule.
- 社団法人日本生物工学会の論文
- 2002-02-25
著者
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Sugiyama Masanori
Dep. Of Molecular Microbiology And Biotechnology Graduate School Of Biomedical Sciences Hiroshima Un
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Sugiyama M
Department Of Molecular Microbiology And Biotechnology Graduate School Of Biomedical Sciences Hirosh
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Sugiyama Masanori
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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Sugiyama Masanori
Institute Of Pharmaceutical Sciences Faculty Of Medicine Hiroshima University
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KUMAGAI Takanori
Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University
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Kumagai Takanori
Institute Of Pharmaceutical Sciences Faculty Of Medicine Hiroshima University
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Sugiyama Masanori
Department Of Molecular Microbiology And Biotechnology Hiroshima University
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Kumagai Takanori
Dep. Of Molecular Microbiology And Biotechnology Graduate School Of Biomedical Sciences Hiroshima Un
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Sugiyama Masanori
Department Of Molecular Microbiology And Biotechnology Graduate School Of Biomedical Sciences Hirosh
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Sugiyama Masanori
Department of Molecular Microbiology and Biotechnology, Graduate School of Biomedical Sciences, Hiroshima University:Frontier Center for Microbiology, Hiroshima University
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