Wu Ling-Ling, Gao Hong-Wen, Gao Nai-Yun, Chen Fang-Fang, Chen Ling
State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, PR China.
BMC Struct Biol. 2009 May 14;9:31. doi: 10.1186/1472-6807-9-31.
Recently, perfluorooctanoic acid (PFOA) has become a significant issue in many aspects of environmental ecology, toxicology, pathology and life sciences because it may have serious effects on the endocrine, immune and nervous systems and can lead to embryonic deformities and other diseases. Human serum albumin (HSA) is the major protein component of blood plasma and is called a multifunctional plasma carrier protein because of its ability to bind an unusually broad spectrum of ligands.
The interaction of PFOA with HSA was investigated in the normal physiological condition by equilibrium dialysis, fluorospectrometry, isothermal titration calorimetry (ITC) and circular dichroism (CD). The non-covalent interaction is resulted from hydrogen bond, van der Waals force and hydrophobic stack. PFOA binding to HSA accorded with two-step binding model with the saturation binding numbers of PFOA, only 1 in the hydrophobic intracavity of HSA and 12 on the exposed outer surface. The interaction of PFOA with HSA is spontaneous and results in change of HSA conformation. The possible binding sites were speculated.
The present work suggested a characterization method for the intermolecular weak interaction. It is potentially useful for elucidating the toxigenicity of perfluorochemicals when combined with biomolecular function effect, transmembrane transport, toxicological testing and the other experiments.
近年来，全氟辛酸（PFOA）在环境生态、毒理学、病理学和生命科学的诸多方面已成为一个重大问题，因为它可能对内分泌、免疫和神经系统产生严重影响，并可导致胚胎畸形和其他疾病。人血清白蛋白（HSA）是血浆中的主要蛋白质成分，因其能够结合异常广泛的配体而被称为多功能血浆载体蛋白。
通过平衡透析、荧光光谱法、等温滴定量热法（ITC）和圆二色性（CD）在正常生理条件下研究了PFOA与HSA的相互作用。非共价相互作用由氢键、范德华力和疏水堆积引起。PFOA与HSA的结合符合两步结合模型，PFOA的饱和结合数为，在HSA的疏水腔内仅1个，在暴露的外表面上有12个。PFOA与HSA的相互作用是自发的，并导致HSA构象的改变。推测了可能的结合位点。
目前的工作提出了一种分子间弱相互作用的表征方法。当与生物分子功能效应、跨膜转运、毒理学测试和其他实验相结合时，它可能有助于阐明全氟化学品的毒性。
