QM/MM Study of the Conversion of Oxophlorin into Verdoheme by Heme Oxygenase

The Journal of Physical Chemistry. B
Fatemeh Sadat AlaviU Ryde

Abstract

Heme oxygenase is an enzyme that degrades heme, thereby recycling iron in most organisms, including humans. Pervious density functional theory (DFT) calculations have suggested that iron(III) hydroxyheme, an intermediate generated in the first step of heme degradation by heme oxygenase, is converted to iron(III) superoxo oxophlorin in the presence of dioxygen. In this article, we have studied the detailed mechanism of conversion of iron(III) superoxo oxophlorin to verdoheme by using combined quantum mechanics and molecular mechanics (QM/MM) calculations. The calculations employed 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. The reaction was found to be exothermic by -35 kcal/mol, with a rate-determining barrier of 19 kcal/mol in the doublet state. The protein environment and especially water in the enzyme pocket significantly affects the reaction by decreasing the reaction activation energies and changing the structures by providing strategic hydrogen bonds.

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Citations

Jun 13, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Fatemeh Sadat AlaviUlf Ryde
Apr 15, 2020·Physical Chemistry Chemical Physics : PCCP·Chang YuanZongchao Jia
Apr 19, 2018·Frontiers in Chemistry·Lili Cao, Ulf Ryde
May 21, 2021·Journal of Molecular Modeling·Hamideh TasharofiParisa Rajabali Jamaat

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