Identification of the source of oxygen in the alkaline-labile product accompanying cytosine release during bleomycin-mediated oxidative degradation of d(CGCGCG)

Rabow, Lois E.; Stubbe, JoAnne; Kozarich, John W.; McGall, Glen H.

doi:10.1021/ja00164a050

Cited by 73 publications

(69 citation statements)

References 4 publications

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“…177 It is known that the DNA products resulting from BLM cleavage incorporate oxygen atoms from solvent water, not the oxidant. 178 However, this does not rule out the involvement of a ferryl intermediate, since the oxygen rebound step may not be kinetically competitive.…”

Section: Bleomycinmentioning

confidence: 99%

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

McLain

Lee

Groves

2000

Biomimetic Oxidations Catalyzed by Transition Metal Complexes

123

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Oxometalloporphyrin Intermediates in Enzymatic ProcessesMetalloenzymes catalyze a host of biological oxidation reactions that are crucial to life processes. The cytochromes P450, an important family of heme-iron metalloenzymes, are oxidoreductases that activate molecular oxygen (O2) and incorporate one of the oxygen atoms into a wide variety of biological substrates, with concurrent two-electron reduction of the other oxygen atom to H 2 0.' The structure, biochemistry, molecular biology and the chemistry of cytochrome P450 and related model systems was extensively reviewed recently. 1 Cytochrome P450 enzymes have been isolated from numerous mammalian tissues (e.g. liver, kidney, lung, intestine and adrenal cortex), as well as insects, plants, yeast and bacteria, 2 and are known to catalyze hydroxylations, epoxidations, N-, S-and O-dealkylations, N-oxidations, sulfoxidations, and dehalogenations. 1 These oxygenation reactions play a central role in carcinogen activation, drug and xenobiotic detoxification, and steroid and prostaglandin metabolism. Surprisingly, the active site of the enzyme, known in detail from several X-ray crystal structures, is extraordinarily simple, with an iron protoporphyrin IX (3.1; Fig. 3.1) buried deep in a hydrophobic, substrate-binding pocket of 91 Biomimetic Oxidations Catalyzed by Transition Metal Complexes Downloaded from www.worldscientific.com by KAINAN UNIVERSITY on 02/20/15. For personal use only.

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Section: Bleomycinmentioning

confidence: 99%

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

McLain

Lee

Groves

2000

Biomimetic Oxidations Catalyzed by Transition Metal Complexes

123

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“…4d,5 DNA cleavage has been especially well characterized, and the mechanism of degradation and derived products have been described in some detail. 6 …”

mentioning

confidence: 99%

Dynamics of Bleomycin Interaction with a Strongly Bound Hairpin DNA Substrate, and Implications for Cleavage of the Bound DNA

et al. 2012

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Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe•BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B2 binding to a strongly bound hairpin DNA, to define the effects of Fe3+, salt and temperature on BLM–DNA interaction. One strong primary DNA binding site, and at least one much weaker site was documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus enhanced binding to a given site does not necessarily result in increased DNA degradation at that site, i.e. for strongly bound DNAs, the facility of DNA cleavage must involve parameters in addition to the intrinsic rate of C-4′ H atom abstraction from DNA sugars.

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“…We have now extended our studies to Fe-BLM bound to the self-complementary hexanucleotides, d(CGCGCG) and d(ATATAT), with the intent of detecting structural changes in the metal binding site that correlate with the sequence specificity of DNA cleavage. The use of hexameric DNA sequences is based on reports that Fe-BLM-mediated cleavage of d(CGCGCG) has been well characterized and shown to occur overwhelmingly at the third deoxycytosine residue from the 5Ј-end (dC-5) (25)(26)(27). Although cleavage of AT sites by Fe-BLM has also been documented, scission at these sites occurs with much lower efficiency (9,10).…”

mentioning

confidence: 99%

Sequence-specific Changes in the Metal Site of Ferric Bleomycin Induced by the Binding of DNA

Sam¹,

Takahashi²,

Lippai³

et al. 1998

Journal of Biological Chemistry

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Identification of the source of oxygen in the alkaline-labile product accompanying cytosine release during bleomycin-mediated oxidative degradation of d(CGCGCG)

Cited by 73 publications

References 4 publications

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

Biomimetic Oxygenations Related to Cytochrome P450: Metal-Oxo and Metal-Peroxo Intermediates

Dynamics of Bleomycin Interaction with a Strongly Bound Hairpin DNA Substrate, and Implications for Cleavage of the Bound DNA

Sequence-specific Changes in the Metal Site of Ferric Bleomycin Induced by the Binding of DNA

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