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Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors
Wang, Ziyun1; Li, Shen2; Sun, Lidan1; Fan, Jianglin2; Liu, Zhenming1
刊名PLOS ONE
2013-08-21
DOI10.1371/journal.pone.0072146
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
WOS记录号WOS:000324470100081
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50284
专题北京大学药学院
北京大学第二临床医学院_国际合作办公室
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
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GB/T 7714
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).
APA Wang, Ziyun,Li, Shen,Sun, Lidan,Fan, Jianglin,&Liu, Zhenming.(2013).Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors.PLOS ONE,8(8).
MLA Wang, Ziyun,et al."Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors".PLOS ONE 8.8(2013).
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