Structure and function of [Fe]-hydrogenase and biosynthesis of the FeGP cofactor

The three known types of hydrogenases catalyze reversible activation of H2 and heterolyticcleavage to a hydride and a proton . [NiFe]- and [FeFe]-hydrogenases furthercleave the hydride to two electrons and a proton. [Fe]-hydrogenase (Hmd), the enzyme covered in this chapter, instead transfers the hydride to a substrate, methenyltetrahydromethanopterin(methenyl-H4MPT+ ) (Figure 6.1) [1, 2]. The free-energy change of this reaction is – 5.5 kJ/mol. The reverse reaction, formation of H2 and methenyl-H4MPT+, is favorable under acidic conditions [3, 4].[Fe]-hydrogenase is involved in the methanogenic pathway of many hydrogenotrophicmethanogenic archaea , including members of the Methanopyrales, Methanobacteriales,and Methanococcales. Under nickel-limiting conditions , [Fe]-hydrogenase isoverproduced and functions as the major hydrogenase enzyme in the methanogenicpathway, in which it provides four electrons [5]. [Fe]-hydrogenase contains a mononucleariron-guanylyl pyridinol (FeGP) cofactor. In the cofactor, the low-spin Fe(II) iscoordinated with two cis-CO and fixed to the organic part, guanylyl pyridinol, withits acyl-carbon and pyridinol-nitrogen; the iron site is covalently bound to a cysteineresidue [1]