The atomic-resolution crystal structure of activated [Fe]-hydrogenase
The atomic-resolution crystal structure of activated [Fe]-hydrogenase
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DOI：
10.1038/s41929-019-0289-4
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发表时间：
2019-06-01
期刊：
影响因子：
37.8
通讯作者：
Shima, Seigo
中科院分区：
文献类型：
--
作者：
Huang, Gangfeng;Wagner, Tristan;Shima, Seigo
氢化酶是构建新型 H-2 催化剂的有前景的模板。 [Fe]-氢化酶具有铁鸟苷基吡啶醇 (FeGP) 辅因子，可催化从 H-2 到次甲基四氢甲烷蝶呤（次甲基-H4MPT+，产甲烷菌中的 C-1 载体）的可逆氢化物转移。在这里，我们基于闭合活性形式的 [Fe]-氢化酶的 1.06 埃分辨率结构，提出了该反应的详细机制场景，其中 FeGP 辅因子的 Fe 位于明显扭曲的次甲基-H4MPT+ 的氢化物接受 C14a 附近。从开放到封闭的转变在排出水配体时产生不饱和五配位 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 2-OH 基团充当催化碱基，并提供了相当完整的 H-2 活化图：发现空 Fe 位点上的 H-2 结合几乎是热中性的，而 H-2 裂解和氢化物转移顺利进行。整个反应涉及扭曲的次甲基-H4MPT+的重新定位和松弛。
Hydrogenases are promising templates for constructing new H-2-based catalysts. [Fe]-hydrogenase, which features an ironguanylylpyridinol (FeGP) cofactor, catalyses a reversible hydride transfer from H-2 to methenyl-tetrahydromethanopterin (methenyl-H4MPT+, a C-1 carrier in methanogens). Here, we present a detailed mechanistic scenario of this reaction based on the 1.06 angstrom 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 H-2 activation: H-2 binding on the empty Fe site was found to be nearly thermo-neutral while H-2 cleavage and hydride transfer proceed smoothly. The overall reaction involves a repositioning and relaxation of the distorted methenyl-H4MPT+.