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Updated: Aug 7, 2026

Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Quantum chemical evaluation of protein control over heme ligation: CO/O2 discrimination in myoglobin
Filippo De Angelis1, Andrzej A Jarzecki, Roberto Car
1Chemistry Department, Princeton University, Princeton, New Jersey 08544, USA.
Abstract:
Control of O2 versus CO binding in myoglobin (Mb) is tuned by a distal histidine residue through steric and H-bonding interactions. These interactions have been evaluated via Car-Parrinello DFT calculations, whose efficiency allows full quantum mechanical treatment of the 13 closest residues surrounding the heme. The small (8 degrees ) deviation of the Fe-C-O bond angle from linearity results from the steric influence of a distal valine residue and not the distal histidine. H-bond energies were evaluated by replacing the distal histidine with the non-H-bonding residue isoleucine. Binding energies for CO and O2 decreased by 0.8 and 4.1 kcal/mol for MbCO and MbO2, in good agreement with experimental H-bond estimates. Ligand discrimination is dominated by distal histidine H-bonding, which is also found to stabilize a metastable side-on isomer of MbO2 that may play a key role in MbO2 photodynamics.
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