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Identification of a copper ion recognition peptide sequence in the subunit II of cytochrome c oxidase: a combined theoretical and experimental study

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Abstract

The role of the pentapeptide, NHSFM, derived from the surface exposed part of the metal ion binding loop of the subunit II of cytochrome c oxidase on the maturation of the binuclear purple CuA center of the enzyme has been investigated using several experimental and computational methods. The copper ion was found to form 1:1 complex of the pentapeptide with a binding constant ~ 104 M−1 to 105 M−1, where a 4 ligand coordination from the peptide in a type 2 copper center was revealed. The pH dependence of the metal–peptide was associated with a \({\text{p}}K_{{\text{a}}}\) of ~ 10 suggesting deprotonation of the N-terminal amine. EXAFS studies as well as DFT calculations of the metal–peptide complexes revealed pH dependent changes in the metal–ligand bond distances. Spectroscopic properties of the metal peptides calculated from TDDFT studies agreed with the experimental results. Restrained molecular dynamics (RMD) simulations indicated coordination of a carbonyl oxygen from the asparagine (N) side chain and of water molecules apart from histidine (H), methionine (M) and terminal amine of asparagine (N) in a distorted square planar geometry of Cu–NHSFM. Analyses of the backbone distances as well as B-factors for the metal peptide suggested that the peptide backbone becomes more compact and rigid on binding of the metal ion. This indicated that binding of copper ion to this pentapeptide in the protein possibly cause movement of the protein backbone bringing other coordinating residues closer to the copper ion, and thus hel** in sequential uptake of copper ions to the protein.

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Acknowledgements

Authors wish to thank Mr Bharat T Kansara for providing technical support, Prof. Ranjan Das and Dr V. Rane in EPR experiments. The financial support was obtained from the Department of Atomic Energy, Government of India, under project identification No. RT14003). The work was carried out at the Tata Institute of Fundamental Research, Mumbai.

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  1. Dwaipayan Dutta Gupta and Imon Mandal contributed equally.

Authors and Affiliations

  1. Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, 400 005, India

    Dwaipayan Dutta Gupta, Imon Mandal, Ravindra Venkatramani & Shyamalava Mazumdar

  2. Atomic and Molecular Physics Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India

    Chandrani Nayak, Shambhu Nath Jha & Dibyendu Bhattacharyya

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  1. Dwaipayan Dutta Gupta
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  2. Imon Mandal
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  3. Chandrani Nayak
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Correspondence to Ravindra Venkatramani or Shyamalava Mazumdar.

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Dutta Gupta, D., Mandal, I., Nayak, C. et al. Identification of a copper ion recognition peptide sequence in the subunit II of cytochrome c oxidase: a combined theoretical and experimental study. J Biol Inorg Chem 26, 411–425 (2021). https://doi.org/10.1007/s00775-021-01867-7

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  • DOI: https://doi.org/10.1007/s00775-021-01867-7

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