Profiling of lysophosphatidylethanolamine molecular species in human serum and in silico prediction of the binding site on albumin
Profiling of lysophosphatidylethanolamine molecular species in human serum and in silico prediction of the binding site on albumin
复制标题
人血清中溶血磷脂酰乙醇胺分子种类的分析以及白蛋白结合位点的计算机预测
DOI：
10.1002/biof.1868
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发表时间：
2022
期刊：
影响因子：
6
通讯作者：
Hui Shu‐Ping
中科院分区：
文献类型：
--
作者：
Inoue Nao;Sakurai Toshihiro;Yamamoto Yusuke;Chiba Hitoshi;Hui Shu‐Ping
溶血磷脂酰乙醇胺（LPE）是由磷脂产生的主要溶血磷脂，并与人血清白蛋白（HSA）结合。LPEs在体内可根据其酰基链的差异发挥各种作用。然而，关于LPEs的生物学功能的报道很少。因此，我们使用液相色谱-串联质谱法确定了健康参与者（n= 8）血清中主要LPE的确切相对丰度。因此，发现LPE 18：2（24.1 ± 5.2%）在血清中最丰富。为了了解LPE的分布，对通过凝胶过滤高效液相色谱法分离的血清进行定量测量。在白蛋白组分中观察到的LPE多于脂蛋白组分。我们还使用AutoDock进行了荧光置换测定和计算机分子对接实验，以确认LPE对HSA的亲和力和结合位点。LPE与HSA上药物位点1和2的结合亲和力相对较低，Ki值分别约为11和3.8 μM。AutoDock分析揭示了与药物位点结合的LPE的构象以及LPE与其他HSA位点结合的可能性。这些发现有助于阐明LPEs的生物学和病理学功能。
Lysophosphatidylethanolamine (LPE) is a major lysophospholipid produced by phospholipids and binds to human serum albumin (HSA). LPEs may play various roles in vivo depending on the differences in their acyl chains. However, only few reports have been published on the biological functions of LPEs. Hence, we determined the exact relative abundance of the major LPEs in the serum of healthy participants (n= 8) using liquid chromatography–tandem mass spectrometry. Consequently, LPE 18:2 (24.1 ± 5.2%) was found to be the most abundant in serum. To understand the distribution of LPEs, the serum separated via gel‐filtration high‐performance liquid chromatography was subjected to quantitative measurement. LPEs were more observed in the albumin fraction than the lipoprotein fraction. We also performed a fluorescence displacement assay and an in silico molecular docking experiment using AutoDock to confirm the affinity and binding sites of the LPEs on HSA. The binding affinities of the LPEs for drug sites 1 and 2 on HSA were relatively low, with Ki values of approximately 11 and 3.8 μM, respectively. AutoDock analysis revealed the conformation of the LPEs bound to drug sites and the possibility of LPEs binding to other HSA sites. These findings could help to elucidate the biological and pathological functions of LPEs.