文章基本信息

标题：Molecular switches of the κ opioid receptor triggered by 6′-GNTI and 5′-GNTI
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作者：Jianxin Cheng ; Xianqiang Sun ; Weihua Li 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
DOI：10.1038/srep18913
出版社：Springer Nature
摘要：The κ opioid receptor ( κ OR) is a member of G-protein-coupled receptors, and is considered as a promising drug target for treating neurological diseases. κ OR selective 6′-GNTI was proved to be a G-protein biased agonist, whereas 5′-GNTI acts as an antagonist. To investigate the molecular mechanism of how these two ligands induce different behaviors of the receptor, we built two systems containing the 5′-GNTI- κ OR complex and the 6′-GNTI- κ OR complex, respectively, and performed molecular dynamics simulations of the two systems. We observe that transmembrane (TM) helix 6 of the κ OR rotates about 4.6^o on average in the κ OR-6′-GNTI complex. Detailed analyses of the simulation results indicate that E297^6.58 and I294^6.55 play crucial roles in the rotation of TM6. In the simulation of the κ OR-5′-GNTI system, it is revealed that 5′-GNTI can stabilize TM6 in the inactive state form. In addition, the kink of TM7 is stabilized by a hydrogen bond between S324^7.47 and the residue V69^1.42 on TM1.