Hydrogenases are enzymes that produce or consume hydrogen gas. Each type of hydrogenase contains, as a minimum, an iron atom, with CO and CN ligands which tune its redox potential and Lewis-acidity to optimize the binding of dihydrogen. The Fe-hydrogenase from methanogenic bacteria is the simplest hydrogenase and catalyzes a direct hydride transfer from H₂ to its organic substrate. All other hydrogenases catalyze reduction of electron acceptors, according to the equation H₂ = H⁺ + 2e⁻. The hydrogen-binding sites are of two types: the [NiFe(Se)]-hydrogenases, which contain a dinuclear center of nickel and iron, and the [FeFe]-hydrogenases, which contain a dinuclear iron site, the H cluster. In each case, the protein is arranged to leave a vacant position in the active site for binding H₂, as well as separate channels for transfer of H₂ and H⁺ to the surface. A chain of iron-sulfur clusters provides a pathway for electrons to a binding site on the surface for electron acceptors and donors. O₂ and CO are inhibitors that bind to the vacant site and block access to H₂; O₂ also causes oxidation of the metal centers and sulfur ligands. Some hydrogenases from aerobic bacteria, which are resistant to this inhibition, are of interest for applications in biofuel cells.