摘要
2009年,斑马鱼P2X4受体的第一个晶体结构的发表是个重要时刻;这是研究人员第一次能够有结构性的解释他们的实验数据。几个研究小组立即着手于利用数据使人们更好地理解哺乳动物P2X受体的分子模型,以便设计和解释的新的,更集中的结构-功能实验的结果。在2012年,斑马鱼的P2X4在ATP结合状态下的晶体结构的发表,进一步阐明了配体结合和其耦合到离子通道活化的机制,发起了一个建模、实验和解释的新循环。本综述的目的是通过突出斑马鱼P2X4晶体结构的优势和局限性,描述我们目前对P2X受体的三维结构的认识,讨论如何从中获得分子模型和它们的用途,解释为什么哺乳动物P2X受体的晶体结构仍然是揭示差动激动剂/拮抗剂效力、变构调节、孔隙扩张和脱敏的分子机制所必需的。
关键词: 晶体结构,分子动力学,分子建模, P2X ,结构 - 功能
Current Medicinal Chemistry
Title:Purinergic P2X Receptors: Structural and Functional Features Depicted by X-Ray and Molecular Modelling Studies
Volume: 22 Issue: 7
Author(s): Leanne Grimes and Mark T. Young
Affiliation:
关键词: 晶体结构,分子动力学,分子建模, P2X ,结构 - 功能
摘要: The publication of the first crystal structures of the zebrafish P2X4 receptor in 2009 was a pivotal moment; for the first time, researchers were able to interpret their experimental data in a structural context. Several research groups immediately set about using the data to make molecular models of the betterunderstood mammalian P2X receptors, in order to design and interpret the results of new, more focused structure- function experiments. In 2012, the publication of the crystal structure of zebrafish P2X4 in the ATPbound state gave further insights into the mechanism of ligand binding and its coupling to ion channel activation, initiating a new cycle of modelling, experimentation and interpretation. The purpose of this review is to describe our current understanding of the 3D-structure of P2X receptors, by highlighting the strengths and limitations of the zebrafish P2X4 crystal structures, discussing how the molecular models derived from them have been made, and what they have been used for, and explaining why crystal structures of mammalian P2X receptors are still needed to uncover the molecular mechanisms of differential agonist/antagonist potency, allosteric modulation, pore dilatation and desensitisation.
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Cite this article as:
Leanne Grimes and Mark T. Young , Purinergic P2X Receptors: Structural and Functional Features Depicted by X-Ray and Molecular Modelling Studies, Current Medicinal Chemistry 2015; 22 (7) . https://dx.doi.org/10.2174/0929867321999141212131457
DOI https://dx.doi.org/10.2174/0929867321999141212131457 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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