[Fe-Fe]-hydrogenase Reactivated by Residue Mutations as Bridging Carbonyl Rearranges: A QM/MM Study.
[Fe-Fe]-hydrogenase Reactivated by Residue Mutations as Bridging Carbonyl Rearranges: A QM/MM Study.
复制标题
[Fe-Fe]-氢化酶通过残基突变作为桥接羰基重排重新激活：QM/MM 研究。
DOI：
10.1002/qua.22381
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发表时间：
2010
影响因子：
2.2
通讯作者：
Gogonea,Valentin
中科院分区：
文献类型：
--
作者：
Motiu,Stefan;Gogonea,Valentin
在这项工作中，我们发现了通过O2或OH再活化外源抑制的[Fe-Fe]-氢化酶的水酶相反应途径，O2或OH代谢成H2O（Dogaru et al.，Int J Quantum Chem 2008，108; Motiu等人，Int J Quantum Chem 2007，107，1248）。我们采用量子力学/分子力学混合方法（QM/MM）研究了外源抑制酶基质的再活化途径。对酶进行的ONIOM计算与实验结果一致（Liu等人，J Am Chem Soc 2002，124，5175），即野生型[Fe-Fe]-氢化酶H-簇被氧代谢物抑制。一个半径为8 μ m（从远端铁，美联储）的酶的球形区域已被筛选的残基，防止H2O离开催化位点，并重新激活[Fe-Fe]-氢化酶H-簇。在筛选过程中，极性残基被去除，一次一个，频率计算提供了水解离的吉布斯能的变化（由于它们的缺失）。当残基缺失导致吉布斯能显著降低时，已经进行了进一步的残基取代。在每次取代之后，进行几何优化和频率计算以评估用于消除H2O的吉布斯能的变化。对单残基去除（GGlu 374 1.6kcal/mol）、单取代（GGlu 374 1.6kcal/mol）和单取代（GGlu 374 1.6kcal/mol）都得到了有利的热力学结果
In this work, we found aqueous enzyme phase reaction pathways for the reactivation of the exogenously inhibited [Fe-Fe]-hydrogenases by O2, or OH, which metabolizes to H2O (Dogaru et al., Int J Quantum Chem 2008, 108; Motiu et al., Int J Quantum Chem 2007, 107, 1248). We used the hybrid quantum mechanics/molecular mechanics (QM/MM) method to study the reactivation pathways of the exogenously inhibited enzyme matrix. The ONIOM calculations performed on the enzyme agree with experimental results (Liu et al., J Am Chem Soc 2002, 124, 5175), that is, wild-type [Fe-Fe]-hydrogenase H-cluster is inhibited by oxygen metabolites. An enzyme spherical region with a radius of 8 Å (from the distal iron, Fed) has been screened for residues that prevent H2O from leaving the catalytic site and reactivate the [Fe-Fe]-hydrogenase H-cluster. In the screening process, polar residues were removed, one at a time, and frequency calculations provided the change in the Gibbs’ energy for the dissociation of water (due to their deletion). When residue deletion resulted in significant Gibbs’ energy decrease, further residue substitutions have been carried out. Following each substitution, geometry optimization and frequency calculations have been performed to assess the change in the Gibbs’ energy for the elimination of H2O. Favorable thermodynamic results have been obtained for both single residue removal (G Glu 374 1.6 kcal/mol), single substitution (GGlu 374