QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase
文献类型：期刊论文
| 作者 | Hou, Q. Q.1; Wang, J. H.1; Gao, J.1; Liu, Y. J.1,2; Liu, C. B.1 |
| 刊名 | biochimica et biophysica acta-proteins and proteomics
 |
| 出版日期 | 2012-04-01 |
| 卷号 | 1824期号:4页码:533-541 |
| 关键词 | QM/MM Epinephrine Methyltransferase Reaction mechanism Mutation |
| ISSN号 | 1570-9639 |
| 中文摘要 | epinephrine is a naturally occurring adrenomedullary hormone that transduces environmental stressors into cardiovascular actions. as the only route in the catecholamine biosynthetic pathway, phenylethanolamine n-methyltransferase (pnmt) catalyzes the synthesis of epinephrine. to elucidate the detailed mechanism of enzymatic catalysis of pnmt, combined quantum-mechanical/molecular-mechanical (qm/mm) calculations were performed. the calculation results reveal that this catalysis contains three elementary steps: the deprotonation of protonated norepinphrine, the methyl transferring step and deprotonation of the methylated norepinphrine. the methyl transferring step was proved to be the rate-determining step undergoing a sn2 mechanism with an energy barrier of 16.4 kcal/mol. during the whole catalysis, two glutamic acids glu185 and glu219 were proved to be loaded with different effects according to the calculations results of the mutants. these calculation results can be used to explain the experimental observations and make a good complementarity for the previous qm study. (c) 2012 elsevier b.v. all rights reserved. |
| 英文摘要 | epinephrine is a naturally occurring adrenomedullary hormone that transduces environmental stressors into cardiovascular actions. as the only route in the catecholamine biosynthetic pathway, phenylethanolamine n-methyltransferase (pnmt) catalyzes the synthesis of epinephrine. to elucidate the detailed mechanism of enzymatic catalysis of pnmt, combined quantum-mechanical/molecular-mechanical (qm/mm) calculations were performed. the calculation results reveal that this catalysis contains three elementary steps: the deprotonation of protonated norepinphrine, the methyl transferring step and deprotonation of the methylated norepinphrine. the methyl transferring step was proved to be the rate-determining step undergoing a sn2 mechanism with an energy barrier of 16.4 kcal/mol. during the whole catalysis, two glutamic acids glu185 and glu219 were proved to be loaded with different effects according to the calculations results of the mutants. these calculation results can be used to explain the experimental observations and make a good complementarity for the previous qm study. (c) 2012 elsevier b.v. all rights reserved. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | biochemistry & molecular biology ; biophysics |
| 研究领域[WOS] | biochemistry & molecular biology ; biophysics |
| 关键词[WOS] | molecular-dynamics ; enzymatic-reactions ; pk(a) values ; adrenaline ; inhibitors ; brain ; binding ; system ; pnmt ; rationalization |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000302443000001 |
| 公开日期 | 2013-03-15 |
| 源URL | [http://ir.nwipb.ac.cn/handle/363003/3696]  |
| 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, Q. Q.,Wang, J. H.,Gao, J.,et al. QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase[J]. biochimica et biophysica acta-proteins and proteomics,2012,1824(4):533-541. |
| APA | Hou, Q. Q.,Wang, J. H.,Gao, J.,Liu, Y. J.,&Liu, C. B..(2012).QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase.biochimica et biophysica acta-proteins and proteomics,1824(4),533-541. |
| MLA | Hou, Q. Q.,et al."QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase".biochimica et biophysica acta-proteins and proteomics 1824.4(2012):533-541. |
入库方式： OAI收割
来源：西北高原生物研究所
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