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首页> 外文期刊>Biochemistry >Lipoprotein-Associated Phospholipase A2 Interacts with Phospholipid Vesicles via a Surface-Disposed Hydrophobic α-Helix
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Lipoprotein-Associated Phospholipase A2 Interacts with Phospholipid Vesicles via a Surface-Disposed Hydrophobic α-Helix

机译：脂蛋白相关的磷脂酶A2通过表面布置的疏水性α-螺旋与磷脂囊泡相互作用

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摘要

Lipoprotein-associated phospholipase A2 (Lp-PLA2) playsnimportant roles in both the inhibition and promotion of inflammation innhuman disease. It catalyzes the hydrolytic inactivation of plasma plateletnactivating factor (PAF) and is also known as PAF acetylhydrolase. Highnlevels of PAF are implicated in a variety of inflammatory diseases such asnasthma, necrotizing enterocolitis, and sepsis. Lp-PLA2 also associates withnlipoproteins in human plasma where it hydrolyzes oxidized phospholipids tonproduce pro-inflammatory lipid mediators that can promote inflammationnand the development of atherosclerosis. Lp-PLA2 plasma levels havenrecently been identified as a biomarker of vascular inflammation, atheroscleroticnvulnerability, and future cardiovascular events. The enzyme is thusna prominent target for the development of inflammation and atherosclerosis-nmodulating therapeutics. While the crystallographically determinednstructure of the enzyme is known, the enzyme’s mechanism of interaction with PAF and the function-modulating lipids innlipoproteins is unknown. We have employed peptide amide hydrogenu0001deuterium exchange mass spectrometry (DXMS) toncharacterize the association of Lp-PLA2 with dimyristoylphosphatidylcholine (DMPC) vesicles and found that specific residuesn113u0001120 in one of the enzyme’s surface-disposed hydrophobic R-helices likely mediate liposome binding.
机译：脂蛋白相关的磷脂酶A2（Lp-PLA2）在抑制和促进人类炎症反应中起着重要作用。它催化血浆血小板活化因子（PAF）水解失活，也称为PAF乙酰水解酶。 PAF的高水平与多种炎性疾病有关，如哮喘，坏死性小肠结肠炎和败血症。 Lp-PLA2还与人血浆中的脂蛋白相关，在脂蛋白中水解氧化的磷脂，从而产生促炎性脂质介体，从而促进炎症和动脉粥样硬化的发展。 Lp-PLA2血浆水平最近已被确定为血管炎症，动脉粥样硬化易损性和未来心血管事件的生物标志物。因此，该酶是炎症和调节动脉粥样硬化的治疗方法发展的主要目标。尽管已知该酶的晶体结构，但该酶与PAF和功能性调节脂类脂蛋白相互作用的机制尚不清楚。我们已利用肽酰胺氢u0001氘交换质谱（DXMS）表征Lp-PLA2与二肉豆蔻酰基磷脂酰胆碱（DMPC）囊泡的缔合，并发现在该酶的表面沉积的疏水性R螺旋之一中的特定残基可能介导脂质体结合。

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  • 来源
    《Biochemistry》 |2011年第23期|p.5314-5321|共8页
  • 作者

    Jian Cao Yuan-Hao Hsu Sheng Li Virgil L. Woods Jr. and Edward A. Dennis;

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    †Department of Chemistry and Biochemistry and Pharmacology, School of Medicine, and ‡Department of Medicine,Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California 92093-0601, United States;

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