CAS OpenIR  > 研究所(批量导入)
Conformational Transition Pathway in the Inhibitor Binding Process of Human Monoacylglycerol Lipase
Alternative TitleProtein J.
Chen, Huayou1,2,3; Tian, Rui1; Ni, Zhong1; Zhang, Zhongge2; Chen, Hongzhang3; Guo, Qi1; Saier, Milton H., Jr.2
2014-12-01
Source PublicationPROTEIN JOURNAL
ISSN1572-3887
Volume33Issue:6Pages:503-511
AbstractHuman monoacylglycerol lipase (MGL) catalyzes the hydrolysis of 2-arachidonoylglycerol to arachidonic and glycerol, which plays a pivotal role in the normal biological processes of brain. Co-crystal structure of the MGL in complex with its inhibitor, compound 1, shows that the helix alpha 4 undergoes large-scale conformational changes in response to the compound 1 binding compared to the apo MGL. However, the detailed conformational transition pathway of the helix alpha 4 in the inhibitor binding process of MGL has remained unclear. Here, conventional molecular dynamics (MD) and nudged elastic band (NEB) simulations were performed to explore the conformational transition pathway of the helix alpha 4. Conventional MD simulations unveiled that the compound 1 induced the closed conformation of the active site of MGL, reduced the conformational flexibility of the helix alpha 4, and elicited the large-scale conformational rearrangement of the helix alpha 4, leading to the complete folding of the helix alpha 4. Moreover, NEB simulations revealed that the conformational transition pathway of helix alpha 4 underwent an almost 180A degrees counter-clockwise rotation of the helix alpha 4. Our computational results advance the structural and mechanistic understanding of the inhibitory mechanism.; Human monoacylglycerol lipase (MGL) catalyzes the hydrolysis of 2-arachidonoylglycerol to arachidonic and glycerol, which plays a pivotal role in the normal biological processes of brain. Co-crystal structure of the MGL in complex with its inhibitor, compound 1, shows that the helix alpha 4 undergoes large-scale conformational changes in response to the compound 1 binding compared to the apo MGL. However, the detailed conformational transition pathway of the helix alpha 4 in the inhibitor binding process of MGL has remained unclear. Here, conventional molecular dynamics (MD) and nudged elastic band (NEB) simulations were performed to explore the conformational transition pathway of the helix alpha 4. Conventional MD simulations unveiled that the compound 1 induced the closed conformation of the active site of MGL, reduced the conformational flexibility of the helix alpha 4, and elicited the large-scale conformational rearrangement of the helix alpha 4, leading to the complete folding of the helix alpha 4. Moreover, NEB simulations revealed that the conformational transition pathway of helix alpha 4 underwent an almost 180A degrees counter-clockwise rotation of the helix alpha 4. Our computational results advance the structural and mechanistic understanding of the inhibitory mechanism.
KeywordMgl Md Simulations Nudged Elastic Band Conformational Transition Pathway
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1007/s10930-014-9572-z
URL查看原文
Indexed BySCI
Language英语
WOS KeywordMOLECULAR-DYNAMICS SIMULATION ; MONOGLYCERIDE LIPASE ; CANNABINOID RECEPTOR ; 2-ARACHIDONOYLGLYCEROL ; INACTIVATION ; HYDROLYSIS ; ENZYME ; ANANDAMIDE ; GSK3-BETA ; MECHANISM
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000345437000001
Citation statistics
Cited Times:4[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/11707
Collection研究所(批量导入)
Affiliation1.Jiangsu Univ, Inst Life Sci, Zhenjiang 212013, Peoples R China
2.Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA
3.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 10090, Peoples R China
Recommended Citation
GB/T 7714
Chen, Huayou,Tian, Rui,Ni, Zhong,et al. Conformational Transition Pathway in the Inhibitor Binding Process of Human Monoacylglycerol Lipase[J]. PROTEIN JOURNAL,2014,33(6):503-511.
APA Chen, Huayou.,Tian, Rui.,Ni, Zhong.,Zhang, Zhongge.,Chen, Hongzhang.,...&Saier, Milton H., Jr..(2014).Conformational Transition Pathway in the Inhibitor Binding Process of Human Monoacylglycerol Lipase.PROTEIN JOURNAL,33(6),503-511.
MLA Chen, Huayou,et al."Conformational Transition Pathway in the Inhibitor Binding Process of Human Monoacylglycerol Lipase".PROTEIN JOURNAL 33.6(2014):503-511.
Files in This Item:
File Name/Size DocType Version Access License
Conformational Trans(3453KB)期刊论文出版稿限制开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Chen, Huayou]'s Articles
[Tian, Rui]'s Articles
[Ni, Zhong]'s Articles
Baidu academic
Similar articles in Baidu academic
[Chen, Huayou]'s Articles
[Tian, Rui]'s Articles
[Ni, Zhong]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Chen, Huayou]'s Articles
[Tian, Rui]'s Articles
[Ni, Zhong]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.