Spectroscopic and computational exploration of hypoxanthine riboside interacting with plasma albumin.
Spectroscopic and computational exploration of hypoxanthine riboside interacting with plasma albumin.
复制标题
DOI：
10.1002/bio.3674
复制
发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
Huaxin Zhang;Dan Zhou;Q. Xia
中科院分区：
文献类型：
--
作者：
Huaxin Zhang;Dan Zhou;Q. Xia
次黄嘌呤核苷(HXR)是一种对摆动碱基对翻译遗传密码必不可少的核苷。在这项工作中，吸收和发光研究表明，HXR与人血清白蛋白(HSA)在基态通过氢键和范德华力形成新的络合物。荧光探针实验表明，HXR进入了人血清白蛋白结构域II的第一个亚区，并与已知的位点标记竞争后被苏德罗定义的位点I上的氨基酸残基所固定。识别作用表现为负的ΔHϴ，ΔSϴ和ΔGϴ热力学参数。荧光光谱和圆二色谱描述了残基的极性以及α-螺旋和β-链含量因HXR结合而发生的变化。通过分子对接方法确定了HXR-HSA复合物的最合理结构，其中包括结合位置、分子取向、相邻氨基酸残基和氢键。此外，还测定了β-环糊精和一些必需金属离子对HSA-HXR体系作用平衡的影响。本研究全面了解了HXR在血液中的转运机制，对理解HXR的生物转化理论和探讨其临床体内半衰期具有重要意义。
Hypoxanthine riboside (HXR) is a nucleoside essential for wobble base pairs to translate the genetic code. In this work, an absorption and luminescence study showed that HXR and human serum albumin (HSA) formed a new complex through hydrogen bonds and van der Waals forces at ground state. Fluorescence probe experiments indicated that HXR entered the first subdomain of domain II in HSA and was fixed by amino acid residues in site I defined by Sudlow, and after competing with a known site marker. The recognition interaction featured negative ΔHϴ , ΔSϴ and ΔGϴ thermodynamic parameters. Fluorescence and circular dichroism spectra described the polarity of residues and α-helix and β-strand content changed because of HXR binding. The most rational structure for the HXR-HSA complex was recommended by the molecular docking method, in which the binding location, molecular orientation, adjacent amino acid residues, and hydrogen bonds were included. In addition, the influence of β-cyclodextrin and some essential metal ions on the balance of the HSA-HXR system interaction was measured. The study gained comprehensive information on the transportation mechanism for HXR in blood, and was of great significance in understanding the theory of HXR biotransformation and in discussing its clinical in vivo half-life.