title: Regioselectivity of H cluster oxidation.
abstract: The H(2)-evolving potential of [FeFe] hydrogenases is severely limited by the oxygen sensitivity of this class of enzymes. Recent experimental studies on hydrogenase from C. reinhardtii point to O(2)-induced structural changes in the [Fe(4)S(4)] subsite of the H cluster. Here, we investigate the mechanistic basis of this observation by means of density functional theory. Unexpectedly, we find that the isolated H cluster shows a pathological catalytic activity for the formation of reactive oxygen species such as O(2)(-) and HO(2)(-). After protonation of O(2)(-), an OOH radical may coordinate to the Fe atoms of the cubane, whereas H(2)O(2) specifically reacts with the S atoms of the cubane-coordinating cysteine residues. Both pathways are accompanied by significant structural distortions that compromise cluster integrity and thus catalytic activity. These results explain the experimental observation that O(2)-induced inhibition is accompanied by distortions of the [Fe(4)S(4)] moiety and account for the irreversibility of this process.
authors: Laboratorium für Physikalische Chemie, ETH Zurich, Wolfgang-Pauli-Strasse 10 8093 Zürich, Switzerland.
authors: Marta K
authors: MK
authors: Bruska
authors: Martin T
authors: MT
authors: Stiebritz
authors: Markus
authors: M
authors: Reiher
mesh_terms: D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction
chemical_list: D006859:Hydrogen