QM-Cluster Model Study of the Guaiacol Hydrogen Atom Transfer and Oxygen Rebound with Cytochrome P450 Enzyme GcoA
QM-Cluster Model Study of the Guaiacol Hydrogen Atom Transfer and Oxygen Rebound with Cytochrome P450 Enzyme GcoA
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DOI：
10.1021/acs.jpcb.0c10761
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发表时间：
2021-03-30
影响因子：
3.3
通讯作者：
DeYonker, Nathan J.
中科院分区：
文献类型：
--
作者：
Cheng, Qianyi;DeYonker, Nathan J.
用密度泛函方法研究了细胞色素P450-还原酶对GcoA对愈创木酚O-脱甲基化的关键步骤。对于每个模型，从不同的愈创木酚取向开始，检查了两条反应路径。根据这项研究，His354、Phe349、Glu249和Pro250残基被发现对在整个反应过程中保持血红素的平面几何形状很重要。在QM簇模型中需要Val241和Gly245残基来为反应中合适的愈创木酚姿势提供疏水口袋。芳香族三联体Phe75、Phe169和Phe395可能是促进愈创木酚迁移到酶活性部位所必需的，但它不会定性地影响所提出的机制的动力学和热力学。RINRUS所建立的所有QM星团模型都与以前的实验工作非常吻合。这项研究为更好地理解GcoA酶促木质素O-脱甲基化生成邻苯二酚衍生物提供了详细的信息。
The key step of the O-demethylation of guaiacol by GcoA of the cytochrome P450-reductase pair was studied with DFT using two 10-residue and three 15-residue QM-cluster models. For each model, two reaction pathways were examined, beginning with a different guaiacol orientation. Based on this study, His354, Phe349, Glu249, and Pro250 residues were found to be important for keeping the heme in a planar geometry throughout the reaction. Val241 and Gly245 residues were needed in the QM-cluster models to provide the hydrophobic pocket for an appropriate guaiacol pose in the reaction. The aromatic triad Phe75, Phe169, and Phe395 may be necessary to facilitate guaiacol migrating into the enzyme active site, but it does not qualitatively affect kinetics and thermodynamics of the proposed mechanism. All QM-cluster models created by RINRUS agree very well with previous experimental work. This study provides details for better understanding enzymatic O-demethylation of lignins to form catechol derivatives by GcoA.