Lipoprotein-associated phospholipase A(2) interacts with phospholipid vesicles via a surface-disposed hydrophobic α-helix.
Lipoprotein-associated phospholipase A(2) interacts with phospholipid vesicles via a surface-disposed hydrophobic α-helix.
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DOI：
10.1021/bi101916w
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发表时间：
2011-06-14
期刊：
影响因子：
2.9
通讯作者：
Dennis EA
中科院分区：
文献类型：
--
作者：
Cao J;Hsu YH;Li S;Woods VL;Dennis EA
脂蛋白相关磷脂酶A2（Lp-PLA 2）在人类疾病中的炎症抑制和促进中起重要作用。催化血浆血小板活化因子（PAF）的水解失活，也称为PAF乙酰水解酶。高水平的PAF与多种炎性疾病如哮喘、坏死性小肠结肠炎和败血症有关。Lp-PLA 2还与人血浆中的脂蛋白结合，在那里它水解氧化磷脂以产生促炎脂质介质，其可以促进炎症和动脉粥样硬化的发展。Lp-PLA 2血浆水平最近被确定为血管炎症、动脉粥样硬化脆弱性和未来心血管事件的生物标志物。因此，该酶是炎症和动脉粥样硬化调节疗法发展的重要靶点。虽然晶体学确定的酶的结构是已知的，酶的PAF和脂蛋白中的功能调节脂质的相互作用的机制是未知的。我们采用肽酰胺氢-氘交换质谱（DXMS）来表征Lp-PLA 2与二肉豆蔻酰磷脂酰胆碱（DMPC）囊泡的缔合，并发现该酶的表面布置的疏水α-螺旋中的一个中的特定残基113-120可能介导脂质体结合。
Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays important roles in both the inhibition and promotion of inflammation in human disease. It catalyzes the hydrolytic inactivation of plasma platelet activating factor (PAF) and is also known as PAF acetylhydrolase. High levels of PAF are implicated in a variety of inflammatory diseases such as asthma, necrotizing enterocolitis and sepsis. Lp-PLA2 also associates with lipoproteins in human plasma where it hydrolyzes oxidized phospholipids to produce pro-inflammatory lipid mediators that can promote inflammation and the development of atherosclerosis. Lp-PLA2 plasma levels have recently been identified as a biomarker of vascular inflammation, atherosclerotic vulnerability, and future cardiovascular events. The enzyme is thus a prominent target for the development of inflammation and atherosclerosis-modulating therapeutics. While the crystallographically-determined structure of the enzyme is known, the enzyme's mechanism of interaction with PAF and the function-modulating lipids in lipoproteins is unknown. We have employed peptide amide hydrogen-deuterium exchange mass spectrometry (DXMS) to characterize the association of Lp-PLA2 with dimyristoyl phosphatidylcholine (DMPC) vesicles, and found that specific residues 113-120 in one of the enzyme's surface-disposed hydrophobic α-helices likely mediate liposome binding.
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影响因子：
4.8
作者：
Hsu, Yuan-Hao;Burke, John E.;Dennis, Edward A.
通讯作者：
Dennis, Edward A.
影响因子：
6.5
作者：
McIntyre, Thomas M.;Prescott, Stephen M.;Stafforini, Diana M.
通讯作者：
Stafforini, Diana M.
DOI：
10.1016/j.bbapap.2010.03.004
发表时间：
2010-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Pan YH;Bahnson BJ
通讯作者：
Bahnson BJ
氢/氘交换MS对蛋白质构象和动力学的分析。
影响因子：
7.4
作者：
Engen, John R.
通讯作者：
Engen, John R.
影响因子：
5.6
作者：
Hamuro, Y;Anand, GS;Woods, VL
通讯作者：
Woods, VL