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QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)

文献类型:期刊论文

作者Zhu, Wenyou1; Liu, Yongjun1,2
刊名theoretical chemistry accounts
出版日期2013-12-27
卷号133期号:2
ISSN号1432-881x
关键词Cyclohexane-1,2-dione (CDO) Cyclohexane-1,2-dione hydrolase (CDH) Reaction mechanism QM/MM Thiamine diphosphate (ThDP)-dependent enzyme
通讯作者liu, yj (reprint author), shandong univ, sch chem & chem engn, key lab colloid & interface chem, minist educ, jinan 250100, shandong, peoples r china.
中文摘要cyclohexane-1,2-dione hydrolase (cdh) catalyzes the conversion of cyclohexane-1,2-dione (cdo) to 6-oxohexanoate. it is the first thiamine diphosphate (thdp)-dependent enzyme that involves a c-c bond ring cleavage of alicyclic compound. in this paper, the detailed catalytic mechanism of cdh has been studied by using quantum mechanics/molecular mechanics approach. since cdo exists in the form of monohydrated ketone in solution, and one of the two hydroxyl groups may exist in its neutral or deprotonated states, the substrate with different protonation states was firstly docked into the active site by using molecular docking. for the neutral form of cdo, only one binding mode (model a) was observed. in model a, the calculated catalytic reaction involves five elementary steps, and the cleavage of c1(cdo)-c2(thdp) bond is the rate-limiting step with the energy barrier of 19.9 kcal/mol. for the deprotonated form of cdo, because any one of the two hydroxyl groups may be deprotonated, two binding modes can be found. but only one docking pose (model b) can lead to the conversion of cdo to 6-oxohexanoate, and the corresponding reaction contains three elementary steps, and two of which correspond to comparable energy barriers (15.2 vs 14.5 kcal/mol). based on our comparison, it is concluded that the c-c bond cleavage is greatly facilitated by the deprotonation of cdo. from the energy point of view, both of the mechanisms derived from models a and b are possible for cdh catalytic reaction.
英文摘要cyclohexane-1,2-dione hydrolase (cdh) catalyzes the conversion of cyclohexane-1,2-dione (cdo) to 6-oxohexanoate. it is the first thiamine diphosphate (thdp)-dependent enzyme that involves a c-c bond ring cleavage of alicyclic compound. in this paper, the detailed catalytic mechanism of cdh has been studied by using quantum mechanics/molecular mechanics approach. since cdo exists in the form of monohydrated ketone in solution, and one of the two hydroxyl groups may exist in its neutral or deprotonated states, the substrate with different protonation states was firstly docked into the active site by using molecular docking. for the neutral form of cdo, only one binding mode (model a) was observed. in model a, the calculated catalytic reaction involves five elementary steps, and the cleavage of c1(cdo)-c2(thdp) bond is the rate-limiting step with the energy barrier of 19.9 kcal/mol. for the deprotonated form of cdo, because any one of the two hydroxyl groups may be deprotonated, two binding modes can be found. but only one docking pose (model b) can lead to the conversion of cdo to 6-oxohexanoate, and the corresponding reaction contains three elementary steps, and two of which correspond to comparable energy barriers (15.2 vs 14.5 kcal/mol). based on our comparison, it is concluded that the c-c bond cleavage is greatly facilitated by the deprotonation of cdo. from the energy point of view, both of the mechanisms derived from models a and b are possible for cdh catalytic reaction.
WOS标题词science & technology ; physical sciences
类目[WOS]chemistry, physical
研究领域[WOS]chemistry
关键词[WOS]diphosphate-dependent enzymes ; keto-enol transformation ; thiamin diphosphate ; crystal-structure ; pk(a) values ; pyruvate decarboxylase ; angstrom resolution ; density ; rationalization ; dynamics
收录类别SCI
语种英语
WOS记录号WOS:000329116300001
公开日期2014-05-09
源URL[http://ir.nwipb.ac.cn/handle/363003/3886]  
专题西北高原生物研究所_中国科学院西北高原生物研究所
作者单位1.Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China
2.Chinese Acad Sci, Northwest Inst Plateau Biol, Xining 810001, Peoples R China
推荐引用方式
GB/T 7714
Zhu, Wenyou,Liu, Yongjun. QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)[J]. theoretical chemistry accounts,2013,133(2).
APA Zhu, Wenyou,&Liu, Yongjun.(2013).QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH).theoretical chemistry accounts,133(2).
MLA Zhu, Wenyou,et al."QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)".theoretical chemistry accounts 133.2(2013).

入库方式: OAI收割

来源:西北高原生物研究所

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