双铜单加氧酶PHM和DβM中氧气活化及底物羟基化机理的理论研究进展
吴 鹏,王斌举*

(厦门大学化学化工学院,固体表面物理化学国家重点实验室,福建 厦门 361005)

碳氢选择性羟基化; 氧气活化; 量子力学; 分子力学; 肽基甘氨酸α羟基化酶; 多巴胺β单加氧酶

Recent progresses in theoretical study of oxygen activation and substrate hydroxylation by binuclear copper monooxygenases PHM and DβM
WU Peng,WANG Binju*

(State Key Laboratory of Physical Chemistry of Solid Surfaces,College of Chemistry and Chemical Engineering,Xiamen University,Xiamen 361005,China)

stereoselective hydroxylation; dioxygen activation; quantum mechanics; molecular mechanics; peptidylglycine α-hydroxylating monooxygenese; dopamine β-monooxygenasedoi:10.6043/j.issn.0438-0479.202006016

DOI: 10.6043/j.issn.0438-0479.202006010

备注

铜是生物体中含量第二多的过渡金属元素.含铜酶的数量和种类众多,在生物体中分布广泛,其普遍参与氧气的传输以及活化、电子转移、底物氧化等重要代谢过程.双铜单加氧酶肽基甘氨酸α羟基化酶(PHM)和多巴胺β单加氧酶(DβM)通过对相应底物C—H键立体选择性羟基化,合成生理学重要的激素和神经递质.尽管对这两种双铜单加氧酶已进行了大量研究,但是针对氧气活化机制以及底物羟基化的中间体仍有很多争议.本文主要总结双铜单加氧酶PHM和DβM中氧气活化以及底物羟基化机理的理论研究进展,并与实验数据进行比较.

Copper is the second most abundant transition metal element in organisms.Copper-containing enzymes are widely distributed in organisms.Most of them are involved in critical metabolic processes,including dioxygen transport and activation,electron transfer and substrate oxidation.The binuclear copper-containing enzymes,peptidylglycine α-hydroxylating monooxygenese(PHM)and dopamine β-monooxygenase(DβM),accomplish the biosynthesis of physiologically important hormones and neurotransmitters by the stereoselective hydroxylation of C—H bond in corresponding substrates.Despite of extensive experimental and computational studies,the mechanisms of dioxygen activation and nature of the active species for substrate hydroxylation are still controversial.Herein,we review the recent progress in the computational study of oxygen activation and substrate hydroxylation by binuclear copper monooxygenases PHM and DβM,and gauge the computed mechanism with experimental data.