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Influence of heme c attachment on heme conformation and potential

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Abstract

Heme c is characterized by its covalent attachment to a polypeptide. The attachment is typically to a CXXCH motif in which the two Cys form thioether bonds with the heme, “X” can be any amino acid other than Cys, and the His serves as a heme axial ligand. Some cytochromes c, however, contain heme attachment motifs with three or four intervening residues in a CX3CH or CX4CH motif. Here, the impacts of these variations in the heme attachment motif on heme ruffling and electronic structure are investigated by spectroscopically characterizing CX3CH and CX4CH variants of Hydrogenobacter thermophilus cytochrome c552. In addition, a novel CXCH variant is studied. 1H and 13C NMR, EPR, and resonance Raman spectra of the protein variants are analyzed to deduce the extent of ruffling using previously reported relationships between these spectral data and heme ruffling. In addition, the reduction potentials of these protein variants are measured using protein film voltammetry. The CXCH and CX4CH variants are found to have enhanced heme ruffling and lower reduction potentials. Implications of these results for the use of these noncanonical motifs in nature, and for the engineering of novel heme peptide structures, are discussed.

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Fig. 1

Reprinted with permission from Kleingardner and Bren [15], Copyright 2015 American Chemical Society

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Reprinted with permission from Kleingardner et al. [40], Copyright 2013 American Chemical Society

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Acknowledgements

This work is supported by the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy, Grant No. DE-FG02-09ER16121.

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Authors and Affiliations

  1. Department of Chemistry, University of Rochester, Rochester, NY, 14627-0216, USA

    Jesse G. Kleingardner & Kara L. Bren

  2. Department of Chemistry and Biochemistry, Messiah College, Mechanicsburg, PA, 17055, USA

    Jesse G. Kleingardner

  3. Department of Chemistry, Boston University, Boston, MA, 02215-2521, USA

    Benjamin D. Levin & Sean J. Elliott

  4. Regional Center of Advanced Technologies and Materials, 17. listopadu 12, 771 46, Olomouc, Czech Republic

    Giorgio Zoppellaro

  5. Department of Biosciences, University of Oslo, PO Box 1066, Blindern, 0316, Oslo, Norway

    K. Kristoffer Andersson

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  1. Jesse G. Kleingardner
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  2. Benjamin D. Levin
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  3. Giorgio Zoppellaro
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  4. K. Kristoffer Andersson
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Correspondence to Kara L. Bren.

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Kleingardner, J.G., Levin, B.D., Zoppellaro, G. et al. Influence of heme c attachment on heme conformation and potential. J Biol Inorg Chem 23, 1073–1083 (2018). https://doi.org/10.1007/s00775-018-1603-3

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