Sulfoxygenation of Active Site Models of [NiFe] and [FeFe] Hydrogenases – A Commentary on Possible Chemical Models of Hydrogenase Enzyme Oxygen Sensitivity



The organometallic active sites in [NiFe]- and [FeFe]H2ases are sensitive to oxygen in varying degrees. The microorganisms that utilize these enzymes for their hydrogen metabolism, and the enzymes themselves, have evolved from a reducing to an oxidizing environment in ways to avoid competition with oxygen, primarily by burying the active site machinery deeply within the protein matrix. In the case of [NiFe]H2ase, biological studies indicate that repair mechanisms exist for reversible O2-inhibition processes. This Microreview explores the possibility that S-oxygenation may represent reparable O-damaged enzyme active sites. Such S-oxygenation has precedent in chemical models for the terminal thiolate sulfur atoms of the nickel site in [NiFe]H2ase as well as the bridging thiolate sulfur in the [FeFe]H2ase active site. A discussion of the processes of O2 damage leading to both reversible and irreversible enzyme inhibition, and reclamation of activity in the H2ases, as explored by various biochemical assays and spectroscopic methods, is also presented.