Understanding the Dynamics of the Structural States of Cannabinoid Receptors and the Role of Different Modulators.
Understanding the Dynamics of the Structural States of Cannabinoid Receptors and the Role of Different Modulators.
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DOI：
10.3390/life12122137
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发表时间：
2022-12-18
期刊：
影响因子：
3.2
通讯作者：
Elokely, Khaled
中科院分区：
文献类型：
--
作者：
Manandhar, Anjela;Haron, Mona H.;Klein, Michael L.;Elokely, Khaled
大麻素受体CB1R和CB2R是G蛋白偶联受体（GPCR）家族的成员。这些受体最近被发现是影响中枢神经系统的疾病的可能治疗靶点。然而，由于已知CB1R具有精神活性副作用，因此其作为药物靶点的潜力受到限制。因此，靶向CB2R已成为最近研究的主要焦点。使用各种分子建模研究，我们分析了本研究中两种CBR的活性，非活性和中间状态。我们对各种大麻素调节剂的结合特性进行了深入研究，包括激动剂，拮抗剂和反向激动剂，以及CBR的所有不同构象状态。这些调节剂的结合效果进行了研究，各种CB结构特征，包括跨膜螺旋的运动，结合腔的体积，内部流体，和重要的GPCR性能。然后，使用体外实验和计算建模，我们研究了维生素E作为脂质调节剂如何影响THC结合。这种对调节剂与CBR结合的比较研究为结构改变和配体亲和力的机制提供了重要的见解，这可以直接帮助合理设计靶向CB1R或CB2R的选择性调节剂。
The cannabinoid receptors CB1R and CB2R are members of the G protein-coupled receptor (GPCR) family. These receptors have recently come to light as possible therapeutic targets for conditions affecting the central nervous system. However, because CB1R is known to have psychoactive side effects, its potential as a drug target is constrained. Therefore, targeting CB2R has become the primary focus of recent research. Using various molecular modeling studies, we analyzed the active, inactive, and intermediate states of both CBRs in this study. We conducted in-depth research on the binding properties of various groups of cannabinoid modulators, including agonists, antagonists, and inverse agonists, with all of the different conformational states of the CBRs. The binding effects of these modulators were studied on various CB structural features, including the movement of the transmembrane helices, the volume of the binding cavity, the internal fluids, and the important GPCR properties. Then, using in vitro experiments and computational modeling, we investigated how vitamin E functions as a lipid modulator to influence THC binding. This comparative examination of modulator binding to CBRs provides significant insight into the mechanisms of structural alterations and ligand affinity, which can directly help in the rational design of selective modulators that target either CB1R or CB2R.
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影响因子：
3.7
作者：
Beard H;Cholleti A;Pearlman D;Sherman W;Loving KA
通讯作者：
Loving KA
影响因子：
7.3
作者：
Pulp, Alan;Bortoff, Katherine;Zhang, Yanan;Seltzman, Herbert;Mathews, James;Snyder, Rodney;Fennell, Tim;Maitra, Rangan
通讯作者：
Maitra, Rangan
人体免疫组织和白细胞亚群中枢和外周大麻素受体的表达
DOI：
10.1111/j.1432-1033.1995.tb20780.x
发表时间：
1995-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GALIEGUE, S;MARY, S;CASELLAS, P
通讯作者：
CASELLAS, P
DOI：
10.1073/pnas.1110499108
发表时间：
2011-11-15
影响因子：
11.1
作者：
Dror, Ron O.;Arlow, Daniel H.;Shaw, David E.
通讯作者：
Shaw, David E.
DOI：
10.1016/j.jbc.2022.101764
发表时间：
2022-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Dutta S;Selvam B;Das A;Shukla D
通讯作者：
Shukla D