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Issue 33, 2017
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Heme isomers substantially affect heme's electronic structure and function

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Inspection of heme protein structures in the protein data bank reveals four isomers of heme characterized by different relative orientations of the vinyl side chains; remarkably, all these have been reported in multiple protein structures. Density functional theory computations explain this as due to similar energy of the isomers but with a sizable (25 kJ mol−1) barrier to interconversion arising from restricted rotation around the conjugated bonds. The four isomers, EE, EZ, ZE, and ZZ, were then investigated as 4-coordinate hemes, as 5-coordinate deoxyhemes, in 6-coordinate O2-adducts of globins and as compound I intermediates typical of heme peroxidases. Substantial differences were observed in electronic properties relevant to heme function: notably, the spin state energy gap of O2-heme adducts, important for fast reversible binding of O2, depends on the isomer state, and O2-binding enthalpies change by up to 16 kJ mol−1; redox potentials change by up to 0.2 V depending on the isomer, and the doublet–quartet energy splitting of compound I, central to “two-state” reactivity, is affected by up to ∼15 kJ mol−1. These effects are consistently seen with three distinct density functionals, i.e. the effects are not method-dependent. Thus, the nature of the isomer state is an important but overlooked feature of heme chemistry and function, and previous and future studies of hemes may be reconsidered in this new context.

Graphical abstract: Heme isomers substantially affect heme's electronic structure and function

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Article information

17 May 2017
29 Jul 2017
First published
01 Aug 2017

Phys. Chem. Chem. Phys., 2017,19, 22355-22362
Article type

Heme isomers substantially affect heme's electronic structure and function

K. P. Kepp, Phys. Chem. Chem. Phys., 2017, 19, 22355
DOI: 10.1039/C7CP03285D

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