Oxygenolysis reaction mechanism of copper-dependent quercetin 2,3-dioxygenase:A density functional theory study  

作　　者：XIE HuJun LEI QunFang FANG WenJun 

机构地区：[1]Department of Applied Chemistry,Zhejiang Gongshang University,Hangzhou 310035,China [2]Department of Chemistry,Zhejiang University,Hangzhou 310028,China

出　　处：《Science China Chemistry》2012年第9期1832-1841,共10页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (21073164,20673098);the Natural Science Foundation of Zhejiang Province (Y4100620);the Research Foundation of the Education Bureau of Zhejiang Province (Y200906517)

摘　　要：The mechanism of the action of copper-dependent quercetin 2,3-dioxygenase （2,3QD） has been investigated by means of hy- brid density functional theory. The 2,3QD enzyme cleaves the O-heterocycle of a quercetin by incorporation of both oxygen atoms into the substrate and releases carbon monoxide. The calculations show that dioxygen attack on the copper complex is energetically favorable. The adduct has a possible near-degeneracy of states between [Cu2＋-（substrate H＋）] and [Cu＋-（sub- strate-H）. ], and in addition the pyramidalized C2 atom is ideally suited for forming a dioxygembridged structure. In the next step, the C3-C4 bond is cleaved and intermediate lnt5 is formed via transition state TS4. Finally, the Oa-Ob and C2-C3 bonds are cleaved, and CO is released in one concerted transition state （TS5） with the barrier of 63.25 and 61.91 k J/tool in the gas phase and protein environments, respectively. On the basis of our proposed reaction mechanism, this is the rate-limiting step of the whole catalytic cycle and is strongly driven by a relatively large exothermicity of 100.86 kJ/mol. Our work provides some valuable fundamental insights into the behavior of this enzyme.The mechanism of the action of copper-dependent quercetin 2,3-dioxygenase(2,3QD) has been investigated by means of hybrid density functional theory.The 2,3QD enzyme cleaves the O-heterocycle of a quercetin by incorporation of both oxygen atoms into the substrate and releases carbon monoxide.The calculations show that dioxygen attack on the copper complex is energetically favorable.The adduct has a possible near-degeneracy of states between [Cu 2+-(substrate-H +)] and [Cu +-(substrate-H).],and in addition the pyramidalized C 2 atom is ideally suited for forming a dioxygen-bridged structure.In the next step,the C 3-C 4 bond is cleaved and intermediate Int 5 is formed via transition state TS 4.Finally,the O a-O b and C 2-C 3 bonds are cleaved,and CO is released in one concerted transition state(TS 5) with the barrier of 63.25 and 61.91 kJ/mol in the gas phase and protein environments,respectively.On the basis of our proposed reaction mechanism,this is the rate-limiting step of the whole catalytic cycle and is strongly driven by a relatively large exothermicity of 100.86 kJ/mol.Our work provides some valuable fundamental insights into the behavior of this enzyme.

关 键 词：quercetin 2 3-dioxygenase DFT calculations catalytic mechanism METALLOENZYMES oxygenolysis 

分 类 号：O641.121[理学—物理化学] X172[理学—化学]