Ascenzi Paolo, Bocedi Alessio, Notari Stefania, Fanali Gabriella, Fesce Riccardo, Fasano Mauro
Istituto Nazionale per le Malattie Infettive I.R.C.C.S. Lazzaro Spallanzani, Via Portuense 292, I-00149 Roma, Italy.
Mini Rev Med Chem. 2006 Apr;6(4):483-9. doi: 10.2174/138955706776361448.
Human serum albumin (HSA), the most prominent protein in plasma, is best known for its extraordinary ligand binding capacity. The three homologous domains of HSA (labeled I, II, and III), each in turn composed of two subdomains (named A and B), give rise to the three-dimensional structure of HSA. This flexible structural organization allows the protein structure to adapt to a variety of ligands. As conformational adaptability of HSA extends well beyond the immediate vicinity of the binding site(s), cooperativity and allosteric modulation arise among binding sites; this makes HSA similar to a multimeric protein. Although kinetic and thermodynamic parameters for ligand binding to HSA calculated by quantitative structure-activity relationship models are in excellent agreement with those obtained in vitro, cooperative and allosteric equilibria between different binding sites and competition between drugs or between drugs and endogenous ligands make difficult the interpretation of HSA binding properties in vivo. Binding of exogenous and endogenous ligands to HSA appears to be relevant in drug therapy and management. Here, the allosteric modulation of drug binding to HSA is briefly reviewed.
人血清白蛋白（HSA）是血浆中最主要的蛋白质，以其非凡的配体结合能力而闻名。HSA的三个同源结构域（分别标记为I、II和III），每个结构域又依次由两个亚结构域（命名为A和B）组成，形成了HSA的三维结构。这种灵活的结构组织使蛋白质结构能够适应多种配体。由于HSA的构象适应性远远超出结合位点的紧邻区域，结合位点之间会出现协同作用和变构调节；这使得HSA类似于多聚体蛋白。尽管通过定量构效关系模型计算得到的配体与HSA结合的动力学和热力学参数与体外实验结果高度一致，但不同结合位点之间的协同和变构平衡以及药物之间或药物与内源性配体之间的竞争使得体内HSA结合特性的解释变得困难。外源性和内源性配体与HSA的结合在药物治疗和管理中似乎具有相关性。在此，简要综述药物与HSA结合的变构调节。
