Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure.
Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure.
复制标题
DOI：
10.3390/ph3030541
复制
发表时间：
2010-03-08
期刊：
影响因子：
--
通讯作者：
Bahnson BJ
中科院分区：
文献类型：
--
作者：
Srinivasan P;Bahnson BJ
血浆血小板活化因子乙酰水解酶（PAF- ah），也称为脂蛋白相关磷脂酶A2 (Lp-PLA2)，是一种VIIA PLA2酶，催化PAF和某些氧化磷脂的水解。尽管PAF-AH作为促动脉粥样硬化酶或抗动脉粥样硬化酶的作用备受争议，但几项研究表明它是心血管疾病的独立标志物。在人类中，大部分血浆PAF-AH与LDL结合，小部分与HDL结合；大多数酶与小密度LDL和VHDL-1亚类有关。一些研究表明，PAF-AH的抗或促动脉粥样硬化倾向可能取决于与之相关的脂蛋白类型。PAF-AH中与LDL和HDL结合所必需的氨基酸残基已被确定。然而，我们对PAF-AH与LDL和HDL的相互作用的理解仍然不完整。在这篇综述中，我们概述了什么是已知的PAF-AH与脂蛋白颗粒的相互作用，我们提出的问题尚未得到回答。最近解决的PAF-AH晶体结构，以及其他人所做的功能工作，被用作建立PAF-AH与脂蛋白颗粒相互作用模型的指导。
Plasma platelet-activating factor acetylhydrolase (PAF-AH), also called lipoprotein-associated phospholipase A2 (Lp-PLA2), is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.