QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase

NWIPB OpenIR

	QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase
	Hou, Q. Q. ; Wang, J. H. ; Gao, J. ; Liu, Y. J. ; Liu, C. B.
	2012-04-01
发表期刊	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS ; Liu, M; Qu, JP; Yang, M; Wang, ZL; Wang, YL; Zhang, YM; Zhang, ZB.QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase,BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(4):533-541
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.; 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.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/36891
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	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, Liu, M; Qu, JP; Yang, M; Wang, ZL; Wang, YL; Zhang, YM; Zhang, ZB.QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase,BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS,2012,1824(4):533-541,2012.
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.
MLA	Hou, Q. Q.,et al."QM/MM studies on the catalytic mechanism of Phenylethanolamine N-methyltransferase".BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (2012).