Characterization of ligand binding sites on the alpha1-acid glycoprotein in humans, bovines and dogs.
Characterization of ligand binding sites on the alpha1-acid glycoprotein in humans, bovines and dogs.
复制标题
DOI：
10.2133/dmpk.17.300
复制
发表时间：
2002-01-01
影响因子：
2.1
通讯作者：
Otagiri, Masaki
中科院分区：
文献类型：
--
作者：
Matsumoto, Kazuaki;Sukimoto, Katsuaki;Otagiri, Masaki
本研究的目的是对3个物种的α(1)-酸性糖蛋白(AGP)的配基结合部位进行分类和鉴定，以了解不同物种在配基结合特性和配基相互作用对蛋白质结合方面的差异。用碱性配体氯丙嗪和金胺O，酸性配体阿胶香豆素和类固醇激素孕酮检测了人、狗和牛AGP的这些特征。用超滤和荧光技术表征相互作用的性质，数据按Kragh-Hansen方法进行分析。通过相互作用的模型分析，人AGP上的配体结合部位至少由3个部分重叠的亚基组成：碱性配体结合部位、酸性配体结合部位和类固醇激素结合部位。此外，狗和牛的AGP都有一个碱性配体结合部位和一个类固醇激素结合部位，这两个部位明显重叠，相互影响。然而，狗和牛的AGP不包含酸性配体结合区。荧光实验结果表明，3种AGP上配体结合袋的疏水性质相似，但其微粘度明显不同。
The goal of this study was to classify and identify the ligand binding sites on alpha(1)-acid glycoprotein (AGP) from 3 species, in order to understand species differences with respect to both ligand binding properties and ligand interaction on protein binding. These characteristics of human, dog and bovine AGP were examined using the basic ligands chlorpromazine and auramine O, the acidic ligand acenocoumarin, and the steroid hormone progesterone. Ultrafiltration and fluorescence techniques were used to characterize the nature of the interactions, and the data were analyzed according to the method of Kragh-Hansen. Using a model analysis of the interaction, the ligand binding site on human AGP consists of at least 3 partially overlapping subsites: a basic ligand binding site, an acidic ligand binding site and a steroid hormone binding site. Moreover, dog and bovine AGP each have a basic ligand binding site and a steroid hormone binding site, which significantly overlap and affect each other. However, dog and bovine AGPs do not contain an acidic ligand binding region. The results of the fluorescence experiments indicate that the hydrophobic nature of the ligand binding pockets on the 3 AGPs are similar, but that their microviscosities are markedly different.