title: Aerobic damage to [FeFe]-hydrogenases: activation barriers for the chemical attachment of O2.
abstract: [FeFe]-hydrogenases are the best natural hydrogen-producing enzymes but their biotechnological exploitation is hampered by their extreme oxygen sensitivity. The free energy profile for the chemical attachment of O2 to the enzyme active site was investigated by using a range-separated density functional re-parametrized to reproduce high-level ab initio data. An activation free-energy barrier of 13 kcal mol(-1) was obtained for chemical bond formation between the di-iron active site and O2, a value in good agreement with experimental inactivation rates. The oxygen binding can be viewed as an inner-sphere electron-transfer process that is strongly influenced by Coulombic interactions with the proximal cubane cluster and the protein environment. The implications of these results for future mutation studies with the aim of increasing the oxygen tolerance of this enzyme are discussed.
authors.affiliation: Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (UK).
authors.forename: Adam
authors.initials: A
authors.lastname: Kubas
authors.forename: David
authors.initials: D
authors.lastname: De Sancho
authors.forename: Robert B
authors.initials: RB
authors.lastname: Best
authors.forename: Jochen
authors.initials: J
authors.lastname: Blumberger
mesh_terms: D006864:Hydrogenase / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D058085:Iron Compounds / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*
chemical_list: D058085:Iron Compounds; D007501:Iron; D006864:Hydrogenase; D010100:Oxygen
keywords: [FeFe]-hydrogenases; ab initio calculations; electron transfer; iron-sulfur clusters; oxygen activation