How do metal ions modulate the rate‐determining electron transfer step in Cytochrome P450 reactions?

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    Cytochrome P450 (CYP450) enzymes have important
    functions related to human health and their reaction rate is dependent
    on the first electron transfer from the reduction partner. Interestingly,
    experimental work showed that this step is highly affected by the
    addition of metal ions. To understand the effect of external
    perturbations on the CYP450 first reduction step, we performed a
    computational study with model complexes in the presence of metal
    and organic ions, solvent molecules and an electric field effect. The
    work shows that these medium-range interactions affect the driving
    force as well as electron transfer rates dramatically. Based on the
    location, distance and direction of the ions/electric field the reaction
    rate values are improved or impaired for catalysis. Calculations on a
    large crystal structure with alkali metal ions bound implicated inhibition
    patterns of the ions; therefore, we predict that active forms of the
    natural CYP450 isozymes will not have more than one alkali metal
    ions bound in the second-coordination sphere. As such the work
    gives insight into the activity of CYP450 enzymes and the effect of
    ions and electric field perturbations on its activity.
    Original languageEnglish
    JournalChemistry – A European Journal
    Early online date6 Aug 2020
    Publication statusE-pub ahead of print - 6 Aug 2020

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology


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