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4DJH

Structure of the human kappa opioid receptor in complex with JDTic

Summary for 4DJH
Entry DOI10.2210/pdb4djh/pdb
DescriptorKappa-type opioid receptor, Lysozyme, (3R)-7-hydroxy-N-{(2S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]-3-methylbutan-2-yl}-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, CITRIC ACID, ... (6 entities in total)
Functional Keywordsjdtic, gpcr newtork, psi-biology, kor, hkor, kop, structural genomics, protein structure initiative, gpcr network, g-protein coupled receptor, gpcr, 7tm, kappa opioid receptor, dynorphin, membrane protein, transmembrane, hormone receptor, hydrolase, hormone receptor-antagonist complex, hormone receptor/antagonist
Biological sourceHomo Sapiens (human, Bacteriophage T4)
More
Cellular locationCell membrane ; Multi-pass membrane protein : P41145
Total number of polymer chains2
Total formula weight110629.66
Authors
Primary citationWu, H.,Wacker, D.,Mileni, M.,Katritch, V.,Han, G.W.,Vardy, E.,Liu, W.,Thompson, A.A.,Huang, X.P.,Carroll, F.I.,Mascarella, S.W.,Westkaemper, R.B.,Mosier, P.D.,Roth, B.L.,Cherezov, V.,Stevens, R.C.
tructure of the human kappa-opioid receptor in complex with JDTic
Nature, 485:327-332, 2012
Cited by
PubMed Abstract: Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and--in the case of κ-opioid receptor (κ-OR)--dysphoria and psychotomimesis. Here we report the crystal structure of the human κ-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 Å resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human κ-OR. Modelling of other important κ-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5'-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure-activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for κ-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human κ-OR.
PubMed: 22437504
DOI: 10.1038/nature10939
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.9 Å)
Structure validation

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