Desulfovibrio desulfuricans iron hydrogenase: the structure shows unusual coordination to an active site Fe binuclear center

Background: Many microorganisms have the ability to either oxidize molecula r hydrogen to generate reducing power or to produce hydrogen in order to re move low-potential electrons, These reactions are catalyzed by two unrelate d enzymes: the Ni-Fe hydrogenases and the Fe-only hydrogenases, Results: We report here the structure of the heterodimeric Fe-only hydrogen ase from Desulfovibrio desulfuricans - the first for this class of enzymes. With the exception of a ferredoxin-like domain, the structure represents a novel protein fold, The so-called H cluster of the enzyme is composed of a typical [4Fe-4S] cubane bridged to a binuclear active site Fe center conta ining putative CO and CN ligands and one bridging 1,3-propanedithiol molecu le, The conformation of the subunits can be explained by the evolutionary c hanges that have transformed monomeric cytoplasmic enzymes into dimeric per iplasmic enzymes. Plausible electron- and protontransfer pathways and a put ative channel for the access of hydrogen to the active site have been ident ified. Conclusions: The unrelated active sites of Ni-Fe and Fe-only hydrogenases h ave several common features: coordination of diatomic ligands to an Fe ion; a vacant coordination site on one of the metal ions representing a possibl e substrate-binding site; a thiolate-bridged binuclear center; and plausibl e proton- and electron-transfer pathways and substrate channels. The diatom ic coordination to Fe ions makes them low spin and favors low redox states, which may be required for catalysis. Complex electron paramagnetic resonan ce signals typical of Fe-only hydrogenases arise from magnetic interactions between the [4Fe-4S] cluster and the active site binuclear center, The pau city of protein ligands to this center suggests that it was imported from t he inorganic world as an already functional unit.