Genes and Proteins Involved in Nickel-Dependent Hydrogenase Expression

The seemingly simple process of hydrogen activation by Ni-containing hydrogenases requires an enzyme with complex redox transition attributes and precision with respect to synthesis of its metal center. The maturation of these enzymes requires a source of nickel oftentimes acquired by concentration of the metal against a gradient, and a battery of maturation accessory proteins to ensure proper metal mobilization and incorporation. Some of the maturation proteins associate with immature hydrogenase during the process, and accessory proteins have roles ranging from sequestering/storing of nickel to serving as chaperones to maintain proper folding presumably during metallocenter incorporation into the large subunit of hydrogenase. The properties and roles of some Ni-metabolizing hydrogenase accessory proteins have similarities to the maturation proteins needed for other nickel-containing enzymes. Indeed, in the gastric pathogen H. phlori, some of the hydrogenase maturation proteins serve the Ni-dependent maturation of urease as well as that for hydrogenase. Sensor-regulator NiFe-hydrogenases are sometimes used to ensure that the primary hydrogenase involved in hydrogen-oxidizing energy generation is synthesized only when the proper redox environment (such as low oxygen and presence of hydrogen) is encountered. Due to the similarities in the mechanisms of Ni-enzyme maturation among different bacteria and among different Ni-enzyme sinks (urease, hydrogenase, carbon monoxide dehy-drogenase), an integrated picture of the requirements for Ni-enzyme maturation should be anticipated within the next few years.