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Spectral features of the ferrous–CO complex in cytochrome P450: a revisit using TDDFT calculations

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Abstract

There are different views in the literature regarding how to interpret the observed spectral features of the ferrous–CO complexes in cytochrome P450 enzymes (P450s). In this work, we applied density functional theory (DFT) and time-dependent DFT (TDDFT) calculations at the B3LYP-D3BJ/def2-TZVP level with a CPCM correction to the ferrous–CO models of P450s as well as of proteins that contain a histidine-ligated heme. Our results support the notion derived from a previously reported iterative extended Hückel calculation that the involvement of the sulfur lone-pair orbital (S(nz)) of the axial cysteine ligand in the electronic excitations gives rise to a spectral anomaly. The Q and the shorter-wavelength Soret (B′) peaks are primarily due to the electronic transitions from the a2u- and S(nz)-type molecular orbitals (MOs), generated via an orbital interaction of fragment orbitals, to the near-degenerate eg-type π* MOs, respectively. The transitions from the a1u-type MO to the eg-type MOs contribute most to the longer wavelength Soret (B) peaks. Both a2u- and S(nz)-type MOs contribute to the B peaks, but the contribution of the latter is greater. When the axial ligand is histidine, the Q and Soret peaks originate essentially from the excitations from the a2u- and a1u-type MOs to the eg-type MOs. The transitions from the b2u-type MOs to the eg-type MOs play the most significant role in the N peaks of such ferrous–CO complexes. Here, the b2u-type MOs have a large contribution from the imidazole π orbital.

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Acknowledgements

H.H. gratefully acknowledges a Changjiang Scholarship (2022TA0006), a university development fund (UDF01001996), and a Warshel Institute for Computational Biology fund (C10120180043).

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  1. Warshel Institute for Computational Biology, School of Life and Health Sciences, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen, 518172, Guangdong, People’s Republic of China

    Hajime Hirao, Songyan Xia & Shuyang Liu

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  1. Hajime Hirao
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  2. Songyan Xia
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  3. Shuyang Liu
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Hirao, H., Xia, S. & Liu, S. Spectral features of the ferrous–CO complex in cytochrome P450: a revisit using TDDFT calculations. J Biol Inorg Chem 28, 57–64 (2023). https://doi.org/10.1007/s00775-022-01985-w

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