[NiFe]-hydrogenase, small subunit (IPR001821)

Short name: NiFe_hydrogenase_ssu

Overlapping homologous superfamilies

Family relationships



Hydrogenases catalyse the reversible oxidation of molecular hydrogen and play a vital role in anaerobic metabolism. Metal-containing hydrogenases are subdivided into three classes: Fe ('iron only') hydrogenases; Ni-Fe hydrogenases; and Ni-Fe-Se hydrogenases [PMID: 3078655]. Hydrogen oxidation is coupled to the reduction of electron acceptors (such as oxygen, nitrate, sulphate, carbon dioxide and fumarate), whereas proton reduction (hydrogen evolution) is essential in pyruvate fermentation or in the disposal of excess electrons.

The Ni-Fe hydrogenases, when isolated, are found to catalyse both hydrogen evolution and uptake, with low-potential multihaem cytochromes, such as cytochrome c3, acting as either electron donors or acceptors, depending on their oxidation state. Both periplasmic (soluble) and membrane-bound hydrogenases are known.

The Ni-Fe hydrogenases are heterodimeric proteins consisting of small (S) and large (L) subunits. The small subunit contains three iron-sulphur clusters (two [4Fe-4S] and one [3Fe-4S]); the large subunit contains a nickel ion [PMID: 1558764]. Small subunits of membrane-bound Ni-Fe hydrogenases contain a C-terminal domain of about 40 residues that is absent in periplasmic forms.

The 3D structure of the Ni-Fe hydrogenase from Desulfovibrio gigas has been determined at 2.85A resolution [PMID: 7854413]. The small subunit consists of two domains, I(S) and II(S). The alpha/beta twisted open sheet structure of the N-terminal I(S) domain is similar to that of flavodoxin; the C-terminal II(S) domain contains two alpha-helices and has no beta-structure. The Fe-S clusters are distributed almost along a straight line, with the [3Fe-4S] cluster located half-way between the two [4Fe-4S] clusters. The two [4Fe-4S] clusters have been termed proximal (prox) and distal (dist), based on their distance to the Ni atom. Domain I(S) binds the [4Fe-4S]prox cluster, while domain II(S) binds the [4Fe-4S]dist and [3Fe-4S] clusters. The [4Fe-4S]prox cluster is coordinated by Cys-17, Cys-20, Cys-112 and Cys-148; [4Fe-4S]dist is coordinated by His-185, Cys-188, Cys-213 and Cys-219; and [3Fe-4S] is coordinated by Cys-228, Cys-246 and Cys-249 [4Fe-4S]dist is the first known example of a [4Fe-4S] cluster in protein structure ligated by a His side chain. A crown of acidic residues surrounds the partially-exposed His-185 and this might provide a recognition site for the redox partner (cytochrome c3) [PMID: 7854413]. A mechanism of electron transfer from the Ni active site through the Fe-S clusters to the cytochrome c3 has been suggested [PMID: 7854413]. The role of the [3Fe-4S] cluster is not clear: its high redox potential and its absence from some homologous hydrogenases put its involvement in electron transfer in doubt [PMID: 7854413].

GO terms

Biological Process

GO:0055114 oxidation-reduction process

Molecular Function

GO:0008901 ferredoxin hydrogenase activity
GO:0051536 iron-sulfur cluster binding

Cellular Component

GO:0009375 ferredoxin hydrogenase complex

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.