Mossbauer study of iron bleomycin and its activation intermediates

R. M. Burger, T. A. Kent, Susan Band Horwitz

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Abstract

Using Mossbauer spectroscopy, we have examined iron-bleomycin in various oxidation states and in complexes with dioxygen or carbon monoxide. Ferrous bleomycin is a high spin ferrous complex. Addition of O2 converts it into an EPR-silent oxygenated complex. Mossbauer studies in strong applied magnetic fields show that oxygenated bleomycin is diamagnetic. At 4.2 K, the quadrupole splitting ΔE(Q) = -2.96 mm/s and the isomer shift δ = 0.16 mm/s suggest that its electronic structure is best described as low spin ferric iron bound to superoxide anion. A single electron reduction yields activated bleomycin, an EPR-active form that still retains oxygen and which is kinetically competent to initiate DNA cleavage. We have produced this complex by exposing ferrous bleomycin to O2 or by reacting ferric bleomycin with H2O2. The Mossbauer spectra give convincing evidence that the iron of activated bleomycin is low spin ferric. The decay of activated bleomycin yields low spin ferric bleomycin, a complex with Mossbauer parameters nearly identical with those reported for ferric cytochrome P-450. Although iron bleomycin does not have a polyaromatic structure like heme, many features of its electronic structure at the iron are very similar to those produced by the sulfur-coordinated heme iron of ferric cytochrome P-450, a protein that catalyzes a similar oxygen-dependent reaction.

Original languageEnglish (US)
Pages (from-to)1559-1564
Number of pages6
JournalJournal of Biological Chemistry
Volume258
Issue number3
StatePublished - 1983

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Bleomycin
Chemical activation
Iron
Oxygen
Heme
Cytochrome P-450 Enzyme System
Electronic structure
Paramagnetic resonance
Mossbauer Spectroscopy
DNA Cleavage
Magnetic Fields
Carbon Monoxide
Sulfur
Superoxides
Mossbauer spectroscopy
Isomers
iron bleomycin
Electrons
Magnetic fields
Oxidation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mossbauer study of iron bleomycin and its activation intermediates. / Burger, R. M.; Kent, T. A.; Band Horwitz, Susan.

In: Journal of Biological Chemistry, Vol. 258, No. 3, 1983, p. 1559-1564.

Research output: Contribution to journalArticle

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