上腺受体的结构
Lukas Helfinger1, Christopher G Tate2
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Handbook of experimental pharmacology
|July 17, 2023
概括
结构生物学已经揭示了78个上腺受体 (AR) 结构,详细介绍了连接体结合和激活机制. 这些关于β-和α-AR的见解使我们更好地了解受体功能和药物开发.
科学领域:
- 结构生物学是结构生物学.
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 第一个上腺受体 (AR) 结构,人类β2-上腺受体 (hβ2AR),于2007年确定.
- 从那时起,使用X射线晶体学和冷电子显微镜 (cryo-EM) 阐明了78个AR结构.
- 这些结构包括所有三种βAR亚型和四种αAR亚型,提供了全面的见解.
研究的目的:
- 为了提供确定上腺受体结构的概述.
- 详细介绍受体激活机制和连接体结合模式.
- 为了比较不同的上腺受体亚家族,并确定常见的连接体-受体相互作用模式.
主要方法:
- 在X射线晶体学.
- 电子冷显微镜 (cryo-EM) 是一种技术.
- 对联体结合状态的结构分析 (对抗剂,激动剂,G蛋白,阿雷斯,纳米体).
主要成果:
- 确定了78个上腺受体结构,揭示了各种不同的形状状态.
- 详细的分子洞察力对19个抗剂和18个激动剂的 ортостерик结合口袋相互作用.
- 对三种小分子全调节器的结合模式的阐释.
- 识别受体激活和传感器合的分子决定因素.
结论:
- 上腺受体结构数据为理解受体激活和信号提供了分子基础.
- 结构洞察力有助于设计针对上腺受体的新疗法.
- 对比分析揭示了上腺受体子家族中保存和独特的特征.
相关概念视频
Adrenergic Receptors (Adrenoceptors): Classification
2.7K
Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors,...
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors,...
2.7K
Adrenergic Receptors: ɑ Subtype
1.6K
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
1.6K
Adrenergic Receptors: β Subtype
1.7K
β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
1.7K
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.1K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.1K
Sympathetic Signaling
1.0K
Sympathetic signaling, a vital part of the autonomic nervous system, plays a crucial role in mobilizing the body's resources in response to stress or emergencies. It involves the transmission of nerve impulses from sympathetic preganglionic fibers to postganglionic fibers. This results in the release of specific neurotransmitters and activation of adrenergic receptors.
Sympathetic preganglionic fibers release the neurotransmitter acetylcholine (ACh) onto the ganglionic neurons in the...
Sympathetic preganglionic fibers release the neurotransmitter acetylcholine (ACh) onto the ganglionic neurons in the...
1.0K
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
928
Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline...
928


