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Solution structure of Fe(II)–azide–bleomycin derived from NMR data: transition from Fe(II)–bleomycin to Fe(II)–azide–bleomycin as derived from NMR data and structural calculations

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Abstract

The coordination cage of the metal center in Fe(II)–bleomycin has been proposed to consist of the secondary amines in β-aminoalanine, the pyrimidinylpropionamide and imidazole rings, and the amide nitrogen in β-hydroxyhistidine as equatorial ligands, and the primary amine in β-aminoalanine and either the carbamoyl group in mannose or a solvent molecule occupying the axial sites. With the aim of supporting or not supporting coordination of a water molecule to the metal center in Fe(II)–bleomycin, the solution structure of Fe(II)–azide–bleomycin has been derived from NMR data. The structural changes that occur in Fe(II)–bleomycin upon azide binding have been monitored by comparing the experimental results with those obtained from the calculated structures for both bleomycin adducts. The results of this investigation strongly support a model of Fe(II)–bleomycin with six endogenous ligands as the most likely structure held in solution by this metallobleomycin in the absence of DNA.

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Acknowledgments

This work was supported by University of Wyoming start-up funds. We thank Tina Yeh (Accelrys, San Diego, CA, USA) for her very valuable guidance during molecular dynamics calculations. Our gratitude also goes to Vladimir Alvarado (University of Wyoming, Department of Petroleum and Chemical Engineering) for reviewing this manuscript and for helpful discussions.

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  1. Department of Chemistry, University of Wyoming, 1000 E. University Avenue, Laramie, WY, 82071, USA

    Teresa Lehmann & Yang Li

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  1. Teresa Lehmann
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  2. Yang Li
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Correspondence to Teresa Lehmann.

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Lehmann, T., Li, Y. Solution structure of Fe(II)–azide–bleomycin derived from NMR data: transition from Fe(II)–bleomycin to Fe(II)–azide–bleomycin as derived from NMR data and structural calculations. J Biol Inorg Chem 17, 761–771 (2012). https://doi.org/10.1007/s00775-012-0894-z

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  • DOI: https://doi.org/10.1007/s00775-012-0894-z

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