NWIPB OpenIR
QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)
Zhu, Wenyou ; Liu, Yongjun ; Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.
2013-12-27
发表期刊THEORETICAL CHEMISTRY ACCOUNTS ; Zhu, WY; Liu, YJ.QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH),THEORETICAL CHEMISTRY ACCOUNTS,2013,133(2):
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.; 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.
文献类型期刊论文
条目标识符http://210.75.249.4/handle/363003/16659
专题中国科学院西北高原生物研究所
推荐引用方式
GB/T 7714
Zhu, Wenyou,Liu, Yongjun,Liu, YJ . QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)[J]. THEORETICAL CHEMISTRY ACCOUNTS, Zhu, WY; Liu, YJ.QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH),THEORETICAL CHEMISTRY ACCOUNTS,2013,133(2):,2013.
APA Zhu, Wenyou,Liu, Yongjun,&Liu, YJ .(2013).QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH).THEORETICAL CHEMISTRY ACCOUNTS.
MLA Zhu, Wenyou,et al."QM/MM study on the catalytic mechanism of cyclohexane-1,2-dione hydrolase (CDH)".THEORETICAL CHEMISTRY ACCOUNTS (2013).
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Zhu, Wenyou]的文章
[Liu, Yongjun]的文章
[Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.]的文章
百度学术
百度学术中相似的文章
[Zhu, Wenyou]的文章
[Liu, Yongjun]的文章
[Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.]的文章
必应学术
必应学术中相似的文章
[Zhu, Wenyou]的文章
[Liu, Yongjun]的文章
[Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Colloid & Interface Chem, Minist Educ, Jinan 250100, Shandong, Peoples R China.]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。