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Regioselectivity of H cluster oxidation
Marta K Bruska1, Martin T Stiebritz, Markus Reiher
1Laboratorium für Physikalische Chemie, ETH Zurich, Wolfgang-Pauli-Strasse 10 8093 Zürich, Switzerland.
[FeFe] hydrogenases are sensitive to oxygen, limiting their H(2) production. This study reveals how oxygen damages the enzyme's active site, explaining its irreversible inhibition.
Area of Science:
- Biochemistry
- Enzymology
- Computational Chemistry
Background:
- Hydrogenases are crucial for hydrogen production but are inhibited by oxygen.
- Oxygen sensitivity is linked to structural changes in the H cluster's [Fe4S4] subsite.
Purpose of the Study:
- Investigate the mechanism of oxygen-induced damage to the [FeFe] hydrogenase H cluster.
- Explain the observed structural changes and irreversible inhibition.
Main Methods:
- Density functional theory (DFT) calculations.
- Modeling of reactive oxygen species interactions with the H cluster.
Main Results:
- The isolated H cluster catalyzes the formation of superoxide (O2-) and hydroperoxide (HO2-).
- Protonated O2- can form radicals coordinating to iron, while H2O2 reacts with sulfur atoms.
- These reactions cause structural distortions, compromising cluster integrity and activity.
Conclusions:
- The H cluster's intrinsic reactivity with oxygen leads to self-damage.
- This explains the experimentally observed O2-induced structural changes and irreversible inhibition of [FeFe] hydrogenases.
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