Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists
文献类型：期刊论文
| 作者 | Liu, DX ; Jiang, HL; Shen, JS; Zhu, WL; Zhao, L; Chen, KX; Ji, RY
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 1999-02 |
| 卷号 | 20期号:2页码:131-136 |
| 关键词 | molecular models pharmaphore map kappa opioid receptors analgesics ligands cell surface receptors structure-activity relationship bacteriorhodopsin |
| ISSN号 | 0253-9756 |
| 文献子类 | Article |
| 英文摘要 | AIM: To study the interaction between rc-opioid receptor and its nonpeptide agonists. METHODS: The "conservation patterns" for G-protein coupled receptors ( GPCR) were used to determine 7 transmembrane (TM) regions. Taking the crystallographic coordinates of bacteriorhodopsin (BR) as the template, the 3D structural model was constructed for 7 TM of kappa-opioid subtype with molecular mechanics (MM) method. Five highly active nonpeptide kappa-opioid agonists were docked into the 7 helices of kappa-opioid receptor to study the ligand-receptor interaction. RESULTS: Four important interactions between U-50488-like agonists and kappa-opioid receptors were drawn according to our modeling study: (I) the protonated pyrrolidine nitrogen of the ligands formed a hydrogen-bond with the carboxyl of Asp138; (2) the carbonyl oxygen of ligands forms a hydrogen bond to the hydroxyl Of Ser187; (3) the aryl groups connected to acylamide of the agonists inserted into a hydrophobic cavity enclosed by residues Val239, Val236, Phe235, Val232, Leu186, and Trp183; (4) the pyrrolidine of the ligands in the complexes was surrounded by Ile290, Asp138, Ile194, Ile135, and Cys131. CONCLUSION: The proposed interaction mechanism is helpful for further mutant experiments and designing novel potent kappa-opioid agonists. |
| WOS关键词 | BIOLOGICAL EVALUATION ; AFFINITY ; DOCKING |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000078533100008 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274754]  |
| 专题 | 药物发现与设计中心 药理学第三研究室 |
| 通讯作者 | Chen, KX |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, DX,Jiang, HL,Shen, JS,et al. Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists[J]. ACTA PHARMACOLOGICA SINICA,1999,20(2):131-136. |
| APA | Liu, DX.,Jiang, HL.,Shen, JS.,Zhu, WL.,Zhao, L.,...&Ji, RY.(1999).Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists.ACTA PHARMACOLOGICA SINICA,20(2),131-136. |
| MLA | Liu, DX,et al."Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists".ACTA PHARMACOLOGICA SINICA 20.2(1999):131-136. |
入库方式： OAI收割
来源：上海药物研究所
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