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学科主题: 药学
题名:
Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors
作者: Wang, Ziyun1; Li, Shen2; Sun, Lidan1; Fan, Jianglin2; Liu, Zhenming1
刊名: PLOS ONE
发表日期: 2013-08-21
DOI: 10.1371/journal.pone.0072146
卷: 8, 期:8
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: SITE-DIRECTED MUTAGENESIS ; PANCREATIC LIPASE ; CATALYTIC-ACTIVITY ; MOLECULAR-MODEL ; GENE FAMILY ; ATHEROSCLEROSIS ; DEFICIENCY ; MUTATION ; RABBITS ; ATHEROGENESIS
英文摘要:

The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investigated the kinetic characteristics for the catalytic residues using a molecular dynamics simulation strategy. To elucidate the molecular interactions and determine potential key residues involved in the binding to lipase inhibitors, we analyzed the binding pockets and binding poses of known inhibitors of the three lipases. We identified the spatial consensus catalytic triad "Ser-Asp-His", a characteristic motif in all three lipases. Furthermore, we found that the spatial characteristics of the binding pockets of the lipase molecules play a key role in ligand recognition, binding poses, and affinities. To the best of our knowledge, this is the first report that systematically builds homology models of all the triglyceride lipase gene subfamily members. Our data provide novel insights into the molecular structures of lipases and their structure-function relationship, and thus provides groundwork for functional probe design towards lipase-based therapeutic inhibitors for the treatment of hyperlipidemia and atherosclerosis.

语种: 英语
所属项目编号: 21272017 ; 20802006 ; 2012AA020308
项目资助者: National Natural Science Foundation of China ; National High Technology Research and Development Program of China
WOS记录号: WOS:000324470100081
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50284
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Univ Yamanashi, Dept Mol Pathol, Interdisciplinary Grad Sch Med & Engn, Kofu, Yamanashi, Japan
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Ziyun,Li, Shen,Sun, Lidan,et al. Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors[J]. PLOS ONE,2013,8(8).
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