Structural requirements at the melatonin receptor
Structural requirements at the melatonin receptor
复制标题
褪黑激素受体的结构要求
DOI：
--
复制
发表时间：
1995
影响因子：
7.3
通讯作者：
D. Lewis
中科院分区：
文献类型：
--
作者：
D. Sugden;N. Chong;D. Lewis
1通过使用放射性标记激动剂2-[125 I]-iodomelatonin（2-[125 I]-aMT），可以在鸡脑膜中检测到松果体激素褪黑激素（5-甲氧基N-乙酰色胺）的高亲和力特异性结合位点。2测定了一些褪黑激素类似物在2-[125 I]-aMT结合位点的亲和力，并与电子结构分析进行了比较，获得了显着的定量关系。3最佳相关性表明结合亲和力与前线轨道能量差ΔE和侧链氮原子最高占据轨道电子密度QNH相关。4这些发现表明，配体结合可能涉及褪黑激素的5-甲氧基和酰胺部分与互补氨基酸残基之间的氢键，以及褪黑激素的吲哚环与受体结合位点中的芳香族氨基酸之间的电荷转移相互作用。5基于克隆的非洲爪蟾褪黑激素受体的预测氨基酸序列和本研究中观察到的定量结构-亲和力关系，提出了一个推定结合位点的分子模型。
1 High affinity, specific binding sites for the pineal hormone, melatonin (5‐methoxy N‐acetyltryptamine) can be detected in chick brain membranes by use of the radiolabeled agonist, 2‐[125I]‐iodomelatonin (2‐[125I]‐aMT). 2 The affinity of a number of analogues of melatonin at the 2‐[125I]‐aMT binding site was determined and compared with an analysis of their electronic structure and significant quantitative relationships obtained. 3 The best correlations indicated that binding affinity was correlated with ΔE, the difference between the frontier orbital energies, and QNH, the electron density in the highest occupied molecular orbital of the side‐chain nitrogen atom. 4 These findings suggest that ligand binding may involve hydrogen bonding between the 5‐methoxy and amide moieties of melatonin and complementary amino acid residues, and charge transfer interactions between the indole ring of melatonin and an aromatic amino acid in the receptor binding site. 5 A molecular model of a putative binding site is proposed based on the predicted amino acid sequence of the cloned Xenopus laevis melanophore melatonin receptor and the quantitative structure‐affinity relationships observed in the present study.
视网膜褪黑激素受体的表征。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Dubocovich,ML
通讯作者：
Dubocovich,ML
DOI：
10.1073/pnas.91.13.6133
发表时间：
1994-06-21
影响因子：
11.1
作者：
EBISAWA, T;KARNE, S;REPPERT, SM
通讯作者：
REPPERT, SM