A QM/MM study on the catalytic mechanism of pyruvate decarboxylase
文献类型：期刊论文
| 作者 | Hou, Qianqian1; Gao, Jun1; Liu, Yongjun1,2; Liu, Chengbu1 |
| 刊名 | theoretical chemistry accounts
 |
| 出版日期 | 2012-10-01 |
| 卷号 | 131期号:10 |
| 关键词 | Pyruvate decarboxylase Decarboxylation Protonation state Combined QM/MM Reaction mechanism |
| ISSN号 | 1432-881x |
| 中文摘要 | pyruvate decarboxylase (pdc) is a typical thiamin diphosphate (thdp)-dependent enzyme with widespread applications in industry. though studies regarding the reaction mechanism of pdc have been reported, they are mainly focused on the formation of thdp ylide and some elementary steps in the catalytic cycle, studies about the whole catalytic cycle of pdc are still not completed. in these previous studies, a major controversy is whether the key active residues (glu473, glu50', asp27', his113', his114') are protonated or ionized during the reaction. to explore the catalytic mechanism and the role of key residues in the active site, three whole-enzyme models were considered, and the combined qm/mm calculations on the nonoxidative decarboxylation of pyruvate to acetaldehyde catalyzed by pdc were performed. according to our computational results, the fundamental reaction pathways, the complete energy profiles of the whole catalytic cycle, and the specific role of key residues in the common steps were obtained. it is also found that the same residue with different protonation states will lead to different reaction pathways and energy profiles. the mechanism derived from the model in which the residues (glu473, glu50', asp27', his113', his114') are in their protonated states is most consistent with experimental observations. therefore, extreme care must be taken when assigning the protonation states in the mechanism study. because the experimental determination of protonation state is currently difficult, the combined qm/mm method provides an indirect means for determining the active-site protonation state. |
| 英文摘要 | pyruvate decarboxylase (pdc) is a typical thiamin diphosphate (thdp)-dependent enzyme with widespread applications in industry. though studies regarding the reaction mechanism of pdc have been reported, they are mainly focused on the formation of thdp ylide and some elementary steps in the catalytic cycle, studies about the whole catalytic cycle of pdc are still not completed. in these previous studies, a major controversy is whether the key active residues (glu473, glu50', asp27', his113', his114') are protonated or ionized during the reaction. to explore the catalytic mechanism and the role of key residues in the active site, three whole-enzyme models were considered, and the combined qm/mm calculations on the nonoxidative decarboxylation of pyruvate to acetaldehyde catalyzed by pdc were performed. according to our computational results, the fundamental reaction pathways, the complete energy profiles of the whole catalytic cycle, and the specific role of key residues in the common steps were obtained. it is also found that the same residue with different protonation states will lead to different reaction pathways and energy profiles. the mechanism derived from the model in which the residues (glu473, glu50', asp27', his113', his114') are in their protonated states is most consistent with experimental observations. therefore, extreme care must be taken when assigning the protonation states in the mechanism study. because the experimental determination of protonation state is currently difficult, the combined qm/mm method provides an indirect means for determining the active-site protonation state. |
| WOS标题词 | science & technology ; physical sciences |
| 类目[WOS] | chemistry, physical |
| 研究领域[WOS] | chemistry |
| 关键词[WOS] | site-directed mutagenesis ; zymomonas-mobilis ; molecular-dynamics ; crystal-structure ; angstrom resolution ; dependent enzymes ; transition-state ; pk(a) values ; diphosphate ; rationalization |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000309862600006 |
| 公开日期 | 2013-03-15 |
| 源URL | [http://ir.nwipb.ac.cn/handle/363003/3602]  |
| 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, Minist Educ, Key Lab Colloid & Interface Chem, Jinan 250100, Shandong, Peoples R China 2.Chinese Acad Sci, NW Inst Plateau Biol, Key Lab Adaptat & Evolut Plateau Biota, Xining 810001, Qinghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hou, Qianqian,Gao, Jun,Liu, Yongjun,et al. A QM/MM study on the catalytic mechanism of pyruvate decarboxylase[J]. theoretical chemistry accounts,2012,131(10). |
| APA | Hou, Qianqian,Gao, Jun,Liu, Yongjun,&Liu, Chengbu.(2012).A QM/MM study on the catalytic mechanism of pyruvate decarboxylase.theoretical chemistry accounts,131(10). |
| MLA | Hou, Qianqian,et al."A QM/MM study on the catalytic mechanism of pyruvate decarboxylase".theoretical chemistry accounts 131.10(2012). |
入库方式： OAI收割
来源：西北高原生物研究所
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