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, 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. |
| 刊名 | 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):
|
| 出版日期 | 2013-12-27 |
| 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.; 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. |
| 源URL | [http://210.75.249.4/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 |
| 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). |
入库方式： OAI收割
来源：西北高原生物研究所
浏览0
下载0
收藏0
其他版本
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。