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QM/MM MD and free energy simulations of the methylation reactions catalyzed by protein arginine methyltransferase PRMT3
Chu, Yuzhuo1,2; Li, Guohui3; Guo, Hong1,4
KeywordProtein Arginine Methyltransferases Product Specificity Qm/mm Md And Free Energy Simulations Reaction Mechanism
Source PublicationCANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE
2013-07-01
DOI10.1139/cjc-2012-0483
Volume91Issue:7Pages:605-612
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences
WOS SubjectChemistry, Multidisciplinary
WOS Research AreaChemistry
WOS KeywordSERINE-CARBOXYL PEPTIDASE ; PRODUCT SPECIFICITY ; MOLECULAR-DYNAMICS ; ENZYME CATALYSIS ; TIGHT-BINDING ; MECHANISM ; RESIDUES ; STABILIZATION ; INSIGHTS ; ORIGINS
AbstractProtein arginine N-methyltransferases (PRMTs) catalyze the transfer of methyl group(s) from S-adenosyl-L-methionine (AdoMet) to the guanidine group of arginine residue in abundant eukaryotic proteins. Two major types of PRMTs have been identified in mammalian cells. Type I PRMTs catalyze the formation of asymmetric omega-N-G, N-G-dimethylarginine (ADMA), while Type II PRMTs catalyze the formation of symmetric omega-N-G, N'(G)-dimethylarginine (SDMA). The two different methylation products (ADMA or SDMA) of the substrate could lead to different biological consequences. Although PRMTs have been the subject of extensive experimental investigations, the origin of the product specificity remains unclear. In this study, quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations are performed to study the reaction mechanism for one of Type I PRMTs, PRMT3, and to gain insights into the energetic origin of its product specificity (ADMA). Our simulations have identified some important interactions and proton transfers involving the active site residues. These interactions and proton transfers seem to be responsible, at least in part, in making the N-eta 2 atom of the substrate arginine the target of the both 1st and 2nd methylations, leading to the asymmetric dimethylation product. The simulations also suggest that the methyl transfer and proton transfer appear to be somehow concerted processes and that Glu326 is likely to function as the general base during the catalysis.
Language英语
WOS IDWOS:000321436200016
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/137535
Collection中国科学院大连化学物理研究所
Affiliation1.Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA
2.Univ Tennessee, Natl Inst Math & Biol Synth, Knoxville, TN 37996 USA
3.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Peoples R China
4.Oak Ridge Natl Lab, UT ORNL Ctr Mol Biophys, Oak Ridge, TN 37830 USA
Recommended Citation
GB/T 7714
Chu, Yuzhuo,Li, Guohui,Guo, Hong. QM/MM MD and free energy simulations of the methylation reactions catalyzed by protein arginine methyltransferase PRMT3[J]. CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE,2013,91(7):605-612.
APA Chu, Yuzhuo,Li, Guohui,&Guo, Hong.(2013).QM/MM MD and free energy simulations of the methylation reactions catalyzed by protein arginine methyltransferase PRMT3.CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE,91(7),605-612.
MLA Chu, Yuzhuo,et al."QM/MM MD and free energy simulations of the methylation reactions catalyzed by protein arginine methyltransferase PRMT3".CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE 91.7(2013):605-612.
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