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  • Title: DNA strand scission by hemin-thiolate complexes as models of cytochrome P-450.
    Author: Sakurai H, Shibuya M, Shimizu C, Akimoto S, Maeda M, Kawasaki K.
    Journal: Biochem Biophys Res Commun; 1986 Apr 29; 136(2):645-50. PubMed ID: 3010988.
    Abstract:
    Hemin-thiolate complexes, as chemical models for cytochrome P-450 monooxygenases, have been shown to cause strand scission of DNA. Circular super-coiled DNA was degraded to open-circular and linear forms by these complexes in 30 min at pH 7.8 under aerobic conditions, the degradation depending on the structure of the thiol ligand and the ratio of thiol ligand to hemin concentration. The relationship between the structure of the thiol ligand and DNA strand cleaving activity was examined. Complete cleavage of DNA was observed by complexes containing TGE and ME at 400-600 moles excess of thiol ligand to hemin, those containing Cys, CysMe, and CysEt at 50-200 moles excess, and those containing MPG, GSH, penta- and nona-peptides at 5-20 moles excess. Complexes containing NACys and MEA caused no cleavage of DNA. Inhibition experiments suggested the involvement of active oxygen species in the cleavage.
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