Building 3D-structural model of kappa opioid receptor and studying its interaction mechanism with dynorphin A(1-8)

	Building 3D-structural model of kappa opioid receptor and studying its interaction mechanism with dynorphin A(1-8)
	Wan, XH; Huang, XQ; Zhou, DH; Jiang, HL; Chen, KX; Chi, ZQ
刊名	ACTA PHARMACOLOGICA SINICA
	2000-08
卷号	21 期号:8 页码:701-708
关键词	molecular dynamics simulation kappa opioid receptors molecular models binding sites dynorphins
ISSN号	0253-9756
文献子类	Article
英文摘要	AIM: To construct the SD-structural model of human kappa opioid receptor (HKOR) and study its interacting mechanism with dynorphin A(1-8) (Dyn8). METHODS: Comparative molecular modeling was applied to build the 7 transmembrane (TM) helical domain of HKOR using the bovine rhodopsin (OPSD) model as a template. Molecular dynamics was performed to minimize the HKOR model and to simulate the SD-structure of Dyn8 based on the NMR results of dynorphin A(1 - 14). The extracellular loops (EL) were built by self-constructed database searching. DOCK4.0 program was performed to construct Dyn8 complex with HKOR. RESULTS: (1) The model of HKOR was obtained and validated by theoretical and experimental data. (2) The Dyn8-HKOR interacting mechanism is reasonably explained: Side chain of residue Asp138 interacts with protonated nitrogen atom at the N-terminal residues of Dyn8 through electrostatic and hydrogen bonding, which play an important role in ligand binding with receptor. (3) Negatively charged amino acids in the second extracelluar loop (EL2) as Asp223 and Glu209 interact with the C-terminal positively charged residues in Dyn8, and Glu209 is a likely determinant of peptide ligand specificity. CONCLUSION: Some amino acid residues positioned in EL2, TM3, TM4, and TM5 form the binding site and therefore determine the selectivity of kappa peptide agonist.
WOS关键词	RESIDUES ; BINDING
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000088658900006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274587]
专题	中国科学院上海药物研究所
通讯作者	Zhou, DH
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	Wan, XH,Huang, XQ,Zhou, DH,et al. Building 3D-structural model of kappa opioid receptor and studying its interaction mechanism with dynorphin A(1-8)[J]. ACTA PHARMACOLOGICA SINICA,2000,21(8):701-708.
APA	Wan, XH,Huang, XQ,Zhou, DH,Jiang, HL,Chen, KX,&Chi, ZQ.(2000).Building 3D-structural model of kappa opioid receptor and studying its interaction mechanism with dynorphin A(1-8).ACTA PHARMACOLOGICA SINICA,21(8),701-708.
MLA	Wan, XH,et al."Building 3D-structural model of kappa opioid receptor and studying its interaction mechanism with dynorphin A(1-8)".ACTA PHARMACOLOGICA SINICA 21.8(2000):701-708.