TY - JOUR AV - public TI - Aerobic Damage to [FeFe]-Hydrogenases: Activation Barriers for the Chemical Attachment of O2. Y1 - 2014/04/14/ EP - 4084 UR - http://dx.doi.org/10.1002/anie.201400534 ID - discovery1424789 IS - 16 N2 - [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. SP - 4081 N1 - © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. VL - 53 KW - [FeFe]-hydrogenases KW - ab initio calculations KW - electron transfer KW - iron-sulfur clusters KW - oxygen activation A1 - Kubas, A A1 - De Sancho, D A1 - Best, RB A1 - Blumberger, J JF - Angew Chem Int Ed Engl ER -