华法林的结合会影响人血清白蛋白苏德罗Ⅰ位点中H242的酸碱平衡。
Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I of human serum albumin.
作者信息
Perry Jennifer L, Goldsmith Michael R, Williams T Richard, Radack Kyle P, Christensen Trine, Gorham Justin, Pasquinelli Melissa A, Toone Eric J, Beratan David N, Simon John D
机构信息
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
出版信息
Photochem Photobiol. 2006 Sep-Oct;82(5):1365-9. doi: 10.1562/2006-02-23-RA-811.
Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration calorimetry (ITC). The structure of the docked warfarin anion (W-) to Site I is similar to that revealed by X-ray crystallography, with a calculated binding constant of 5.8 x 10(5) M(-1). ITC experiments (pH 7.13 and I = 0.1) carried out in three different buffers (MOPs, phosphate and Tris) reveal binding of W- is accompanied by uptake of 0.30+/-0.02 protons from the solvent. This measurement suggests that the binding of W- is stabilized by an ion-pair interaction between protonated H242 and the phenoxide group of W-.
人血清白蛋白（HSA）的苏德洛位点I位于该蛋白质的IIA亚结构域中，是多种配体的结合腔。在本研究中，使用计算技术和等温滴定量热法（ITC）研究了华法林（W）的结合情况。对接至位点I的华法林阴离子（W-）的结构与X射线晶体学揭示的结构相似，计算得到的结合常数为5.8×10⁵ M⁻¹。在三种不同缓冲液（MOPs、磷酸盐和Tris）中进行的ITC实验（pH 7.13，离子强度I = 0.1）表明，W-的结合伴随着从溶剂中摄取0.30±0.02个质子。该测量结果表明，W-的结合通过质子化的H242与W-的酚氧基之间的离子对相互作用而得以稳定。
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