Hydrogenases and H⁺-Reduction in Primary Energy Conservation

Abstract

Hydrogenases are metalloenzymes subdivided into two classes that contain iron-sulfur clusters and catalyze the reversible oxidation of hydrogen gas (H₂ ⇆ 2H⁺ + 2e⁻). Two metal atoms are present at their active center: either a Ni and an Fe atom in the [NiFe]hydrogenases, or two Fe atoms in the [FeFe]hydrogenases. They are phylogenetically distinct classes of proteins. The catalytic core of [NiFe]hydrogenases is a heterodimeric protein associated with additional subunits in many of these enzymes. The catalytic core of [FeFe]hydrogenases is a domain of about 350 residues that accommodates the active site (H cluster). Many [FeFe]hydrogenases are monomeric but possess additional domains that contain redox centers, mostly Fe–S clusters. A third class of hydrogenase, characterized by a specific iron-containing cofactor and by the absence of Fe–S cluster, is found in some methanogenic archaea; this Hmd hydrogenase has catalytic properties different from those of [NiFe]- and [FeFe]hydrogenases.

The [NiFe]hydrogenases can be subdivided into four subgroups: (1) the H₂ uptake [NiFe]hydrogenases (group 1); (2) the cyanobacterial uptake hydrogenases and the cytoplasmic H₂ sensors (group 2); (3) the bidirectional cytoplasmic hydrogenases able to bind soluble cofactors (group 3); and (4) the membrane-associated, energy-converting, H₂ evolving hydrogenases (group 4). Unlike the [NiFe]hydrogenases, the [FeFe]hydrogenases form a homogeneous group and are primarily involved in H₂ evolution.

This review recapitulates the classification of hydrogenases based on phylogenetic analysis and the correlation with hydrogenase function of the different phylogenetic groupings, discusses the possible role of the [FeFe]hydrogenases in the genesis of the eukaryotic cell, and emphasizes the structural and functional relationships of hydrogenase subunits with those of complex I of the respiratory electron transport chain.