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Molecular modeling of adenosine receptors. The ligand binding site on the rat adenosine A2A receptor.腺苷受体的分子建模。大鼠腺苷A2A受体上的配体结合位点。
Eur J Pharmacol. 1994 Jun 15;268(1):95-104. doi: 10.1016/0922-4106(94)90124-4.
2
Molecular modeling of adenosine receptors. I. The ligand binding site on the A1 receptor.腺苷受体的分子模拟。I. A1受体上的配体结合位点。
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Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition.人A2A腺苷受体的第三个和第七个跨膜螺旋结构域中的亲水性侧链是配体识别所必需的。
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A carboxyl-terminally truncated mutant and nonglycosylated A2a adenosine receptors retain ligand binding.一种羧基末端截短的突变体和非糖基化的A2a腺苷受体保留配体结合能力。
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Identification of domains of the human A1 adenosine receptor that are important for binding receptor subtype-selective ligands using chimeric A1/A2a adenosine receptors.利用嵌合A1/A2a腺苷受体鉴定人A1腺苷受体中对结合受体亚型选择性配体至关重要的结构域。
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Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2a adenosine receptor.定点诱变确定了参与人A2a腺苷受体配体识别的残基。
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Glutamate residues in the second extracellular loop of the human A2a adenosine receptor are required for ligand recognition.人A2a腺苷受体第二个细胞外环中的谷氨酸残基是配体识别所必需的。
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Molecular modeling the human A1 adenosine receptor and study of the mechanisms of its selective ligand binding.人类A1腺苷受体的分子建模及其选择性配体结合机制的研究
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1
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Molecular modeling of the human A2a adenosine receptor.人类A2a腺苷受体的分子建模
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International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors.国际药理学联合会。二十五。腺苷受体的命名和分类。
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4
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Mutagenesis reveals structure-activity parallels between human A2A adenosine receptors and biogenic amine G protein-coupled receptors.诱变研究揭示了人类A2A腺苷受体与生物胺G蛋白偶联受体之间的结构-活性相似性。
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Eur J Pharmacol. 1996 Aug 29;310(2-3):269-72. doi: 10.1016/0014-2999(96)00495-5.
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8
Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition.人A2A腺苷受体的第三个和第七个跨膜螺旋结构域中的亲水性侧链是配体识别所必需的。
Mol Pharmacol. 1996 Sep;50(3):512-21.
9
Glutamate residues in the second extracellular loop of the human A2a adenosine receptor are required for ligand recognition.人A2a腺苷受体第二个细胞外环中的谷氨酸残基是配体识别所必需的。
Mol Pharmacol. 1996 Apr;49(4):683-91.
10
A binding site model and structure-activity relationships for the rat A3 adenosine receptor.大鼠A3腺苷受体的结合位点模型及构效关系
Mol Pharmacol. 1994 Jun;45(6):1101-11.

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Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists.8-苯乙烯基黄嘌呤作为A2选择性腺苷拮抗剂的构效关系
J Med Chem. 1993 May 14;36(10):1333-42. doi: 10.1021/jm00062a005.
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Binding-site modeling of the muscarinic m1 receptor: a combination of homology-based and indirect approaches.毒蕈碱型m1受体的结合位点建模：基于同源性和间接方法的结合
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Projection structure of rhodopsin.视紫红质的投射结构。
Nature. 1993 Apr 22;362(6422):770-2. doi: 10.1038/362770a0.
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A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists.胆囊收缩素B/胃泌素受体的单个氨基酸决定了对非肽类拮抗剂的特异性。
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Role of histidine residues in agonist and antagonist binding sites of A1 adenosine receptor.组氨酸残基在A1腺苷受体激动剂和拮抗剂结合位点中的作用。
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The probable arrangement of the helices in G protein-coupled receptors.G蛋白偶联受体中螺旋的可能排列方式。
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Functional characterization of the A2b adenosine receptor in NIH 3T3 fibroblasts.NIH 3T3成纤维细胞中A2b腺苷受体的功能特性
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A simple method for displaying the hydropathic character of a protein.一种展示蛋白质亲水性特征的简单方法。
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A comprehensive set of sequence analysis programs for the VAX.一套适用于VAX的综合序列分析程序。
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N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine and its uronamide derivatives. Novel adenosine agonists with both high affinity and high selectivity for the adenosine A2 receptor.
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腺苷受体的分子建模。大鼠腺苷A2A受体上的配体结合位点。

Molecular modeling of adenosine receptors. The ligand binding site on the rat adenosine A2A receptor.

作者信息

IJzerman A P, van der Wenden E M, van Galen P J, Jacobson K A

机构信息

Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, The Netherlands.

出版信息

Eur J Pharmacol. 1994 Jun 15;268(1):95-104. doi: 10.1016/0922-4106(94)90124-4.

DOI:10.1016/0922-4106(94)90124-4
PMID:7925617
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6939755/
Abstract

The amino acid sequence of the rat adenosine A2A receptor and the atomic coordinates of bacteriorhodopsin were combined to generate a three-dimensional model for the adenosine A2A receptor. This model consists of seven amphipathic alpha-helices, forming a pore that is rather hydrophilic compared to the hydrophobic outside of the protein. Subsequently, a highly potent and selective ligand for this receptor, 2-(cyclohexylmethylidinehydrazino)adenosine (SHA 174), was docked into this cavity. A binding site is proposed that takes into account the conformational characteristics of the ligand. Moreover, it involves two histidine residues that were shown to be important for ligand coordination from chemical modification studies. Subsequently, the deduced binding site was used to model other potent ligands, including 8-(3-chlorostyryl)caffeine, a new A2-selective antagonist, that could all be accommodated consistent with earlier biochemical and pharmacological findings. Finally, some thoughts on how adenosine receptor activation might proceed are put forward, based on structural analogies with the enzyme family of serine proteases.

摘要

将大鼠腺苷A2A受体的氨基酸序列与细菌视紫红质的原子坐标相结合，生成了腺苷A2A受体的三维模型。该模型由七个两亲性α螺旋组成，形成一个与蛋白质疏水外部相比相当亲水的孔道。随后，将该受体的一种高效且选择性的配体2-(环己基亚甲基肼基)腺苷(SHA 174)对接至该腔体内。提出了一个考虑配体构象特征的结合位点。此外，它涉及两个组氨酸残基，化学修饰研究表明这两个残基对配体配位很重要。随后，推导得到的结合位点被用于模拟其他强效配体，包括新型A2选择性拮抗剂8-(3-氯苯乙烯基)咖啡因，所有这些配体都能与早期的生化和药理学研究结果相一致地容纳在该模型中。最后，基于与丝氨酸蛋白酶酶家族的结构类比，提出了关于腺苷受体激活可能如何进行的一些想法。