Comparative analysis of interactions between aryl hydrocarbon receptor ligand binding domain with its ligands: a computational study

IF 2.222 Q3 Biochemistry, Genetics and Molecular Biology

BMC Structural Biology Pub Date : 2018-12-06 DOI:10.1186/s12900-018-0095-2

Kumaraswamy Naidu Chitrala, Xiaoming Yang, Prakash Nagarkatti, Mitzi Nagarkatti

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引用次数: 15

Abstract

Aryl hydrocarbon receptor (AhR) ligands may act as potential carcinogens or anti-tumor agents. Understanding how some of the residues in AhR ligand binding domain (AhRLBD) modulate their interactions with ligands would be useful in assessing their divergent roles including toxic and beneficial effects. To this end, we have analysed the nature of AhRLBD interactions with 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), 6-formylindolo[3,2-b]carbazole (FICZ), indole-3-carbinol (I3C) and its degradation product, 3,3′-diindolylmethane (DIM), Resveratrol (RES) and its analogue, Piceatannol (PTL) using molecular modeling approach followed by molecular dynamic simulations.

Results showed that each of the AhR ligands, TCDD, FICZ, I3C, DIM, RES and PTL affect the local and global conformations of AhRLBD.

The data presented in this study provide a structural understanding of AhR with its ligands and set the basis for its functions in several pathways and their related diseases.

Abstract Image

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芳烃受体配体结合域与其配体相互作用的比较分析:计算研究

芳烃受体(AhR)配体可能是潜在的致癌物或抗肿瘤剂。了解AhR配体结合域(AhRLBD)中的一些残基如何调节它们与配体的相互作用，将有助于评估它们的不同作用，包括毒性和有益作用。为此，我们利用分子建模方法和分子动力学模拟分析了AhRLBD与2,3,7,8-四氯二苯并-ρ-二恶英(TCDD)、6-甲酰基lindolo[3,2-b]咔唑(FICZ)、吲哚-3-甲醇(I3C)及其降解产物3,3 ' -二吲哚基甲烷(DIM)、白藜芦醇(RES)及其类似物picetanol (PTL)的相互作用性质。结果表明，AhR配体TCDD、FICZ、I3C、DIM、RES和PTL对AhRLBD的局部和全局构象均有影响。本研究提供的数据提供了AhR及其配体的结构理解，并为其在几种途径及其相关疾病中的功能奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Structural Biology 生物-生物物理

CiteScore

3.60

自引率

0.00%

发文量

期刊介绍： BMC Structural Biology is an open access, peer-reviewed journal that considers articles on investigations into the structure of biological macromolecules, including solving structures, structural and functional analyses, and computational modeling.