Classification and phylogeny of hydrogenases

Hydrogenases (H 2ases) catalyze the reversible oxidation of molecular hydrogen and play a central role in microbial energy metabolism. Most of these enzymes are found in Archaea and Bacteria, but a few are present in Eucarya as well. They can be distributed into three classes: the [Fe]-H 2ases, the [NiFe]-H 2ases, and the metal-free H 2ases. The vast majority of known H 2ases belong to the first two classes, and over 100 of these enzymes have been characterized genetically and/or biochemically. Compelling evidence from sequences and structures indicates that the [NiFe]- and [Fe]-H 2ases are phylogenetically distinct classes of proteins. The catalytic core of the [NiFe]-H 2ases is a heterodimeric protein, although additional subunits are present in many of these enzymes. Functional classes of [NiFe]-H 2ases have been defined, and they are consistent with categories defined by sequence similarity of the catalytic subunits. The catalytic core of the [Fe]-H 2ases is a ca. 350-residue domain that accommodates the active site (H-cluster). A few monomeric [Fe]-H 2ases are barely larger than the H-cluster domain. Many others are monomeric as well, but possess additional domains that contain redox centers, mostly iron–sulfur. Some [Fe]-H 2ases are oligomeric. The modular structure of H 2ases is strikingly illustrated in recently unveiled sequences and structures. It is also remarkable that most of the accessory domains and subunits of H 2ases have counterparts in other redox complexes, in particular NADH-ubiquinone oxidoreductase (Complex I) of respiratory chains. Microbial genome sequences are bringing forth a significant body of additional H 2ase sequence data and contribute to the understanding of H 2ase distribution and evolution. Altogether, the available data suggest that [Fe]-H 2ases are restricted to Bacteria and Eucarya, while [NiFe]-H 2ases, with one possible exception, seem to be present only in Archaea and Bacteria. H 2ase processing and maturation involve the products of several genes which have been identified and are currently being characterized in the case of the [NiFe]-H 2ases. In contrast, near to nothing is known regarding the maturation of the [Fe]-H 2ases. Inspection of the currently available genome sequences suggests that the [NiFe]-H 2ase maturation proteins have no similar counterparts in the genomes of organisms possessing [Fe]-H 2ases only. This observation, if confirmed, would be consistent with the phylogenetic distinctiveness of the t