The Role of Nickel in Hydrogenases: Implications for a Heterodinuclear Active Site

Hydrogenases (H2ases) are enzymes that catalyze the reversible two-electron redox chemistry of H2. Most (but not all) H2ases are now known to contain Ni, which is intimately associated with unusual epr signals that are characteristic of the enzymes. A recent crystal structure of the H2ase from Desulfovibrio gigas reveals that the Ni in these enzymes is not an isolated metal center, but part of a Ni, Fe dinuclear cluster. The structure of the biological Ni, Fe cluster is compared with those of model complexes, and the redox chemistry of the model systems is examined for mechanistic insights into the role played by the active site cluster. Coupled with biophysical studies designed to probe the role of the Ni center, these studies fail to provide support for schemes that involve Ni-centered redox chemistry or utilize Ni as a binding site for the substrate (H2) or for inhibitors like CO. Instead, they point to the involvement of the cysteinate ligands and/or the Fe center in the catalysis of H2 redox chemistry.