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首页> 外文期刊>RSC Advances >A comparative binding mechanism between human serum albumin and α-1-acid glycoprotein with corilagin: biophysical and computational approach
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A comparative binding mechanism between human serum albumin and α-1-acid glycoprotein with corilagin: biophysical and computational approach

机译：用核糖蛋白的人血清白蛋白和α-1-酸糖蛋白的比较结合机制：生物物理和计算方法

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The binding of corilagin with plasma serum proteins like human serum albumin (HSA) and α-1-acid glycoprotein (AGP) was investigated under physiological conditions. To understand the pharmacological importance of the corilagin molecule, anti-inflammatory activity on mouse macrophages (RAW 264.7) cell lines was studied. This study reveals that corilagin caused an increase in inhibition growth of inflamed macrophages in concentration-dependent manner with an IC _(50) value of 66 μM. Further, intrinsic fluorescence of HSA and AGP was quenched upon titration of corilagin, and the binding constants obtained from fluorescence emission was found to be K _(corilagin) 4.2 ± 0.02 × 10 ~(5) M ~(?1) which corresponds to the free energy of ?7.6 kcal M ~(?1) at 25 °C for a HSA–corilagin complex. Interestingly, corilagin showed binding with AGP, an acute phase protein, and the binding constant was found to be K _(corilagin) = 1.5 ± 0.01 × 10 ~(4) M ~(?1) and its free energy was ?5.6 kcal M ~(?1) at 25 °C. Further, the average binding distance, r , between the donor (HSA) and acceptor (corilagin) was calculated and found to be 1.32 nm according to F?rster's theory of non-radiation energy transfer. Later, circular dichroism studies emphasized that there are marginal changes in secondary structural conformation of HSA in the presence of corilagin. Corilagin is specifically bound to site I of HSA which was proved by site specific marker, phenylbutazone. Furthermore, the binding details between corilagin and HSA revealed that corilagin was bound to subdomain IIA through multiple interactions like hydrogen bonding and hydrophobic effects. Molecular dynamic studies (MD) also suggest that binding is very precise to site I (IIA domain) on HSA. Also, MD studies showed that HSA–corilagin complex reaches equilibration state at around 4 ns, which proves that the HSA–corilagin complex is stable in nature, hence the experimental and computational results are in agreement. Thus, examining the interaction mechanism of corilagin with plasma proteins may play a critical role in developing corilagin inspired drugs.
机译：在生理条件下研究了与血浆血清蛋白质如人血清白蛋白（HSA）和α-1-酸糖蛋白（AGP）的结合。为了了解核心分子分子的药理重要性，研究小鼠巨噬细胞的抗炎活性（原始264.7）细胞系。本研究表明，核苷酸导致浓度依赖性方式抑制巨噬细胞的抑制生长，IC _（50）值为66μm。此外，在依赖核心滴定时淬灭HSA和AGP的固有荧光，并且发现从荧光发射获得的结合常数是K _（核素）4.2±0.02×10〜（5）m〜（Δ1），其对应于在25℃下为HSA-Corilagin复合物在25℃下的自由能α.7.6kcal m〜（α1）。有趣的是，Corilagin与AGP，急性相蛋白质和结合常数显示结合K _（核素）= 1.5±0.01×10〜（4）M〜（α1），其自由能为5.6千卡M〜（α1）在25°C。此外，根据Fα的非辐射能量转移理论，计算供体（HSA）和受体（Corilagin）之间的平均结合距离R，R，rese为1.32nm。后来，循环二中间主义研究强调，在Corilagin存在下HSA的二级结构构象的边际变化。 Corilagin特异性地与HSA的位点I合并，其由现场特异性标记，苯基丁嗪证明。此外，Corilagin和HSA之间的结合细节显示Corilagin通过氢键和疏水效应等多次相互作用与亚域IIa结合。分子动态研究（MD）还表明，HSA上的网站I（IIA域）非常精确。此外，MD研究表明，HSA-Corilagin复合物在约4ns左右达到平衡状态，证明HSA-Corilagin复合物本质上是稳定的，因此实验和计算结果是一致的。因此，检查与血浆蛋白质的核素的相互作用机理可能在发展核心菌蛋白激发药物中发挥关键作用。

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