Fe-only hydrogenases are enzymes that catalyze dihydrogen production or oxidation, due to the presence of an unusual Fe6S6 cluster (the so-called H-cluster) in their active site, which is composed of a Fe2S2 subsite, directly involved in catalysis, and a classical Fe4S4 cubane cluster. Here, we present a hybrid quantum mechanical and molecular mechanical (QM/MM) investigation of the Fe-only hydrogenase from Desulfovibrio desulfuricans, in order to unravel key issues regarding the activation of the enzyme from its completely oxidized inactive state (H-ox(inac)) and the influence of the protein environment on the structural and catalytic properties of the H-cluster. Our results show that the Fe2S2 subcluster in the (FeFeII)-Fe-II redox statewhich is experimentally observed for the completely oxidized form of the enzymebinds a water molecule to one of its metal centers. The computed QM/MM energy values for water binding to the diferrous subsite are in fact over 70 kJ mol(-1); however, the affinity toward water decreases by 1 order of magnitude after a one-electron reduction of H-ox(inact), thus leading to the release of coordinated water from the H-cluster. The investigation of a catalytic cycle of the Fe-only hydrogenase that implies formation of a terminal hydride ion and a di(thiomethyl)amine (DTMA) molecule acting as an acid/base catalyst indicates that all steps have reasonable reaction energies and that the influence of the protein on the thermodynamic profile of H-2 production catalysis is not negligible. QM/MM results show that the interactions between the Fe2S2 subsite and the protein environment could give place to structural rearrangements of the H-cluster functional for catalysis, provided that the bidentate ligand that bridges the iron atoms in the binuclear subsite is actually a DTMA residue.
Greco, C., Bruschi, M., De Gioia, L., & Ryde, U. (2007). A QM/MM investigation of the activation and catalytic mechanism of Fe-only hydrogenases. INORGANIC CHEMISTRY, 46(15), 5911-5921.
|Citazione:||Greco, C., Bruschi, M., De Gioia, L., & Ryde, U. (2007). A QM/MM investigation of the activation and catalytic mechanism of Fe-only hydrogenases. INORGANIC CHEMISTRY, 46(15), 5911-5921.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||A QM/MM investigation of the activation and catalytic mechanism of Fe-only hydrogenases|
|Autori:||Greco, C; Bruschi, M; De Gioia, L; Ryde, U|
|Data di pubblicazione:||giu-2007|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/ic062320a|
|Appare nelle tipologie:||01 - Articolo su rivista|