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QM/MM study of the conversion of biliverdin into verdoheme by heme oxygenase

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Abstract

It has been shown that after production of oxophlorin, the first step of intermediate, both production of biliverdin and production of verdoheme occur simultaneously (Alavi et al. in Dalton Trans 47:8283–8291, 2018). So the mechanism that converts biliverdin into verdoheme is the subject of some controversy. The detailed conversion of verdoheme to biliverdin was demonstrated before by the Jerusalem group, using combined quantum mechanical and molecular mechanical (QM/MM) calculations. Conversion of iron biliverdin to iron verdoheme in the presence of H+ was investigated using the B3LYP method and the def2-QZVP basis set, considering dispersion effects with the DFT-D3 approach, obtaining accurate energies with large QM regions of almost 1000 atoms. Two spin states, singlet and triplet, were considered for the conversion of biliverdin to verdoheme. The reactant and product are triplet and singlet in their ground states, respectively. The potential energy surface suggests that a spin inversion takes place during the course of reaction after TS2. The ring closing process is exothermic by 5.8 kcal/mol with a kinetic barrier of 16.5 kcal/mol. The activation barrier for removing OH from the ring to produce iron verdoheme is estimated to be 23.2 kcal/mol.

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Acknowledgements

This investigation has been supported by grants from the research council of Shahid Beheshti University and the Swedish research council (Project 2014-5540). The computations were performed on computer resources provided by the Swedish National Infrastructure for Computing (SNIC) at Lunarc at Lund University and HPC2N at Umeå University.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, G.C., Evin, Tehran, 19839-6313, Iran

    Fatemeh Sadat Alavi, Mansour Zahedi & Nasser Safari

  2. Department of Theoretical Chemistry, Chemical Centre, Lund University, P.O. Box 124, 221 00, Lund, Sweden

    Ulf Ryde

Authors
  1. Fatemeh Sadat Alavi
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  2. Mansour Zahedi
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  3. Nasser Safari
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  4. Ulf Ryde
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Correspondence to Mansour Zahedi.

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Alavi, F.S., Zahedi, M., Safari, N. et al. QM/MM study of the conversion of biliverdin into verdoheme by heme oxygenase. Theor Chem Acc 138, 72 (2019). https://doi.org/10.1007/s00214-019-2461-y

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