Comprehensive reaction mechanisms at and near the Ni–Fe active sites of [NiFe] hydrogenases

Abstract

[NiFe] hydrogenase (H₂ase) catalyzes the oxidation of dihydrogen to two protons and two electrons and/or its reverse reaction. For this simple reaction, the enzyme has developed a sophisticated but intricate mechanism with heterolytic cleavage of dihydrogen (or a combination of a hydride and a proton), where its Ni–Fe active site exhibits various redox states. Recently, thermodynamic parameters of the acid–base equilibrium for activation–inactivation, a new intermediate in the catalytic reaction, and new crystal structures of [NiFe] H₂ases have been reported, providing significant insights into the activation–inactivation and catalytic reaction mechanisms of [NiFe] H₂ases. This Perspective provides an overview of the reaction mechanisms of [NiFe] H₂ases based on these new findings.