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G 蛋白偶联受体作为治疗靶点。

G protein-coupled receptors as therapeutic target.

机构信息

Department of Cell Biology and Development, Institute of Cell Physiology, Universidad Nacional Autónoma de México.

Department of Reproduction Biology, Division of Biological and Health Sciences, Universidad Autónoma Metropolitana Campus Iztapalapa. Mexico City, Mexico.

出版信息

Gac Med Mex. 2022;158(2):98-103. doi: 10.24875/GMM.M22000648.

Abstract

Receptors are proteins coded by DNA, some of which have already been crystalized, thus allowing the details of their structure at the atomic level and some aspects of their function to be known. This review focuses on the most diverse and abundant family of receptors, G protein-coupled receptors. This family of receptors recognizes and mediates the action of several endogenous ligands (hormones, neurotransmitters, growth factors and local hormones) and also intervenes in the pathogenesis of various diseases, which is why they are targeted by approximately 30 to 40% of medications that are used in daily clinical practice and of various illegal drugs as well. X-ray crystallography is one of the essential tools that has allowed to observe the structure of these receptors in the amino acids that participate in this interaction, which allows to know the binding site of the endogenous ligand and of synthetic molecules that act on them to modulate their action. Molecular modeling or "docking" is also a computational bioinformatics tool that supports research on receptor-ligand binding, which allows the design and development of increasingly specific drugs. These developments have brought along significant changes in fundamental pharmacodynamic concepts.

摘要

受体是由 DNA 编码的蛋白质,其中一些已经被结晶,从而使我们能够了解它们在原子水平上的结构细节和某些功能方面的知识。本篇综述主要聚焦于种类最多、数量最丰富的受体家族——G 蛋白偶联受体。这类受体能够识别和介导多种内源性配体(激素、神经递质、生长因子和局部激素)的作用,还参与多种疾病的发病机制,这就是为什么大约 30%到 40%的日常临床实践中使用的药物以及各种非法药物都将其作为靶点。X 射线晶体学是一种必不可少的工具,它可以观察参与这种相互作用的氨基酸中这些受体的结构,从而了解内源性配体和作用于它们以调节其作用的合成分子的结合位点。分子建模或“对接”也是一种支持受体-配体结合研究的计算生物信息学工具,它可以用于设计和开发越来越具有特异性的药物。这些进展带来了基础药效学概念的重大变化。

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