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Why is the molybdenum-substituted tungsten-dependent formaldehyde ferredoxin oxidoreductase not active? A quantum chemical study

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Abstract

Formaldehyde ferredoxin oxidoreductase is a tungsten-dependent enzyme that catalyzes the oxidative degradation of formaldehyde to formic acid. The molybdenum ion can be incorporated into the active site to displace the tungsten ion, but is without activity. Density functional calculations have been employed to understand the incapacitation of the enzyme caused by molybdenum substitution. The calculations show that the enzyme with molybdenum (Mo-FOR) has higher redox potential than that with tungsten, which makes the formation of the MoVI=O complex endothermic by 14 kcal/mol. Following our previously suggested mechanism for this enzyme, the formaldehyde substrate oxidation was also investigated for Mo-FOR using the same quantum-mechanics-only model, except for the displacement of tungsten by molybdenum. The calculations demonstrate that formaldehyde oxidation occurs via a sequential two-step mechanism. Similarly to the tungsten-catalyzed reaction, the MoVI=O species performs the nucleophilic attack on the formaldehyde carbon, followed by proton transfer in concert with two-electron reduction of the metal center. The first step is rate-limiting, with a total barrier of 28.2 kcal/mol. The higher barrier is mainly due to the large energy penalty for the formation of the MoVI=O species.

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Acknowledgments

R.-Z.L. acknowledges helpful discussions with Fahmi Himo at Stockholm University, careful revision of the manuscript by the editor, and a postdoctoral fellowship from the Max Planck Society.

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  1. Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany

    Rong-Zhen Liao

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Correspondence to Rong-Zhen Liao.

Electronic supplementary material

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775_2012_961_MOESM1_ESM.pdf

Supplementary material 1. Supporting information available. Cartesian coordinates for all stationary points for formaldehyde oxidation by Mo-FOR. This material is available free of charge via the Internet. (PDF 339 kb)

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Liao, RZ. Why is the molybdenum-substituted tungsten-dependent formaldehyde ferredoxin oxidoreductase not active? A quantum chemical study. J Biol Inorg Chem 18, 175–181 (2013). https://doi.org/10.1007/s00775-012-0961-5

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  • DOI: https://doi.org/10.1007/s00775-012-0961-5

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