Comparative molecular modeling on 3D-structure of opioid receptor-like 1 receptor

	Comparative molecular modeling on 3D-structure of opioid receptor-like 1 receptor
	Huang, XQ ; Jiang, HL; Luo, XM; Chen, KX; Zhu, YC ; Ji, RY ; Cao, Y
刊名	ACTA PHARMACOLOGICA SINICA
	2000-06
卷号	21 期号:6 页码:529-535
关键词	frog rhodopsin ORL1 receptors templates molecular models molecular mechanics
ISSN号	0253-9756
文献子类	Article
英文摘要	AIM: To build the three-dimensional structure of opioid receptor-like 1 (ORL1) receptor. METHODS: Structural elements of ORL1 receptor were predicted from sequence alignments of opioid and related receptors of G protein-coupled receptor (GPCR) based on (i) the consensus, biophysical interpretations of alignment-derived properties, and (ii) tertiary structural homology to frog rhodopsin; The extracellular loops of ORL1 were built by self-constructed database searching based on geometrical constraints; initial model was refined computationally with energy minimization by molecular mechanics method. RESULTS: The calculated structure of ORL1 receptor has clusters of hydrogen bonds existing in interhelices and extracellular loops; the ORL1 receptor has a possible ligand-binding "crevice" situated on the extraside of the transmembrane domains between helices 3, 5, 6, and 7, which is partially covered by the extracellular loop 2 (EL-2); The binding cavity may consist of a "highly conserved region" involving the residues of Asp130, Tyr131, and an outer "conservatively variable region containing the residues near the interface of transmembrane (TM) helices-EL loops; The molecular model obtained is qualitatively consistent with ligand affinities, hy brid peptide studies, and other experimental data. CONCLUSION: The structural model of ORL1 receptor from this study is helpful for clarifying experimental observations of ligands interacting with opioid receptors, and for designing new biological investigations.
WOS关键词	SITE-DIRECTED MUTAGENESIS ; ORPHANIN FQ RECEPTOR ; RECOGNITION ; NOCICEPTIN ; RESIDUES ; PROTEIN ; ORL1
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000087561300007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274612]
专题	中国科学院上海药物研究所
通讯作者	Chen, KX
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.Suzhou Univ, Dept Chem, Suzhou 215006, Peoples R China
推荐引用方式 GB/T 7714	Huang, XQ,Jiang, HL,Luo, XM,et al. Comparative molecular modeling on 3D-structure of opioid receptor-like 1 receptor[J]. ACTA PHARMACOLOGICA SINICA,2000,21(6):529-535.
APA	Huang, XQ.,Jiang, HL.,Luo, XM.,Chen, KX.,Zhu, YC.,...&Cao, Y.(2000).Comparative molecular modeling on 3D-structure of opioid receptor-like 1 receptor.ACTA PHARMACOLOGICA SINICA,21(6),529-535.
MLA	Huang, XQ,et al."Comparative molecular modeling on 3D-structure of opioid receptor-like 1 receptor".ACTA PHARMACOLOGICA SINICA 21.6(2000):529-535.