17α-乙炔基雌二醇与人血清白蛋白的作用机制研究

Interaction mechanism between 17α-ethinyl estradiol and human serum albumin

运用多种光谱方法结合分子模拟技术研究了17α-乙炔基雌二醇(EE2)与人血清白蛋白(HSA)的结合机制。结果表明,EE2通过静态猝灭机制与HSA形成基态复合物,EE2主要结合在HSA亚域IIA的Site I位点,并与氨基酸残基Lys195,Lys199,His288和His242发生作用。25℃下EE2与HSA的结合常数为6.85×10^(4)L/mol,氢键和疏水相互作用为该结合的主要驱动力。巯基含量的增加和α-螺旋含量的减少表明EE2的结合使HSA的二级结构变得伸展。分子动力学模拟进一步阐明了EE2的结合对HSA结构稳定性的影响。

The interaction mechanism of 17α-ethinyl estradiol(EE2)with human serum albumin(HSA)was investigated through multispectral methods combined with molecular docking and molecular dynamics simulation.The results showed that EE2 formed a ground state complex with HSA through a static quenching mechanism.EE2 mainly bound to site I of HSA subdomain IIA and interacted with the amino acid residues Lys195,Lys199,His288 and His242.The binding constant at 25℃was 6.85×10^(4)L/mol,and the binding was driven by hydrogen bonds and hydrophobic interactions.An increase in sulfhydryl content and a decrease inα-helix content suggested that the binding of EE2 to HSA resulted in the structural loosening of HSA.Moreover,molecular dynamics simulation further illuminated the stability of HSA structure in the presence of EE2.