Interaction between bisphenol derivatives and protein disulphide isomerase (PDI) and inhibition of PDI functions: Requirement of chemical structure for binding to PDI
Interaction between bisphenol derivatives and protein disulphide isomerase (PDI) and inhibition of PDI functions: Requirement of chemical structure for binding to PDI
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DOI：
10.1093/jb/mvn075
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发表时间：
2008-09-01
影响因子：
2.7
通讯作者：
Imaoka, Susumu
中科院分区：
文献类型：
--
作者：
Hashimoto, Shoko;Okada, Kazushi;Imaoka, Susumu
双酚A（BPA）是一种内分泌干扰化学品，已报告了几种生物效应。以前，蛋白质二硫化物异构酶（PDI）被分离为双酚A的靶分子。在这项研究中，为了阐明BPA对PDI功能的影响，我们研究了BPA衍生物的化学结构与对PDI介导的异构酶和伴侣活性的影响之间的关系。我们还研究了PDI异构酶结构域的变化对化学品结合的影响，使用PDI突变体和氧化或还原的PDI。在六种化学物质中，只有具有酚基的化学物质可以与PDI结合，并且这些化学物质对PDI介导的异构酶活性也具有抑制作用。PDI异构酶结构域的结构变化不影响化学结合活性。另一方面，本研究中使用的化学物质对PDI的分子伴侣活性影响较小。异构酶活性位点的Cys残基（Cys398和Cys401）中的取代改变了伴侣活性。目前的研究表明，酚类化合物特异性结合PDI和抑制异构酶活性。本研究为预测化学物质的生物学效应和含化学结合功能的PDI的结构研究提供了有用的信息。
Bisphenol A (BPA) is an endocrine disrupting chemical and several biological effects have been reported. Previously, protein disulphide isomerase (PDI) was isolated as a target molecule of bisphenol A. In this study, to clarify the effects of BPA on PDI functions, we investigated the relationship between the chemical structure of BPA derivatives and the effects on PDI-mediated isomerase and chaperone activity. We also investigated the effects of changes in the isomerase domain of PDI on the binding of chemicals, using PDI mutants and oxidized or reduced PDI. Among six chemicals, only chemicals, which have a phenol group, can bind to PDI and these chemicals also have an inhibitory effect on PDI-mediated isomerase activity. Changes in the structure of the PDI isomerase domain did not affect chemical-binding activity. On the other hand, the chemicals used in this study have low effects on chaperone activity of PDI. Substitutions in Cys residues (Cys398 and Cys401) of the isomerase active site changed chaperone activity. The present study indicates that phenolic compounds specifically bind to PDI and inhibit isomerase activity. This study provides useful information to predict the biological effects of chemicals and structural studies of PDI containing the function of chemical binding.