Hydrogenases are promising templates for constructing new H₂-based catalysts. [Fe]-hydrogenase, which features an iron-guanylylpyridinol (FeGP) cofactor, catalyses a reversible hydride transfer from H₂ to methenyl-tetrahydromethanopterin (methenyl-H₄MPT⁺, a C₁ carrier in methanogens). Here, we present a detailed mechanistic scenario of this reaction based on the 1.06 Å resolution structure of [Fe]-hydrogenase in a closed active form, in which the Fe of the FeGP cofactor is positioned near the hydride-accepting C14a of a remarkably distorted methenyl-H₄MPT⁺. The open-to-closed transition generates an unsaturated pentacoordinated Fe on expulsion of a water ligand. Quantum mechanics/molecular mechanics computations based on experimental models indicate that a deprotonated 2-OH group on the FeGP cofactor acts as a catalytic base and provides a fairly complete picture of H₂ activation: H₂ binding on the empty Fe site was found to be nearly thermo-neutral while H₂ cleavage and hydride transfer proceed smoothly. The overall reaction involves a repositioning and relaxation of the distorted methenyl-H₄MPT⁺.

氢化酶是用于构建新的基于H ₂的催化剂的有希望的模板。[Fe]-氢化酶具有铁-胍基吡啶（FeGP）辅助因子，可催化氢化物从H ₂转移至亚甲基-四氢甲基蝶呤（亚甲基-H ₄ MPT ⁺，产甲烷菌中的C ₁载体）。在这里，我们基于封闭活性形式的[Fe]-加氢酶的1.06Å分辨率结构，给出了该反应的详细机理，其中FeGP辅因子的Fe位于显着变形的氢化物接受C14a附近。亚甲基-H ₄ MPT ⁺。开-关过渡在驱出水配体时产生不饱和五配位的Fe。基于实验模型的量子力学/分子力学计算表明，FeGP辅因子上的去质子化的2-OH基团起着催化碱的作用，并提供了相当完整的H ₂活化图：发现在空的Fe位点上的H ₂结合是几乎热中性，而H ₂裂解和氢化物转移平稳进行。整个反应涉及变形的亚甲基-H ₄ MPT ⁺的重新定位和松弛。