Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

6PT3

Crystal structure of the active delta opioid receptor in complex with the small molecule agonist DPI-287

Summary for 6PT3
Entry DOI10.2210/pdb6pt3/pdb
DescriptorDelta opioid receptor, 4-[(R)-[(2S,5R)-4-benzyl-2,5-dimethylpiperazin-1-yl](3-hydroxyphenyl)methyl]-N,N-diethylbenzamide (2 entities in total)
Functional Keywordsmembrane protein, g protein-coupled receptor, gpcr, dop, dor, agonist, active dop-dpi-287 structure, lcp, membrane protein-agonist complex, membrane protein/agonist
Biological sourceHomo sapiens (Human)
Total number of polymer chains2
Total formula weight103089.52
Authors
Primary citationClaff, T.,Yu, J.,Blais, V.,Patel, N.,Martin, C.,Wu, L.,Han, G.W.,Holleran, B.J.,Van der Poorten, O.,White, K.L.,Hanson, M.A.,Sarret, P.,Gendron, L.,Cherezov, V.,Katritch, V.,Ballet, S.,Liu, Z.J.,Muller, C.E.,Stevens, R.C.
Elucidating the active delta-opioid receptor crystal structure with peptide and small-molecule agonists.
Sci Adv, 5:eaax9115-eaax9115, 2019
Cited by
PubMed Abstract: Selective activation of the δ-opioid receptor (DOP) has great potential for the treatment of chronic pain, benefitting from ancillary anxiolytic and antidepressant-like effects. Moreover, DOP agonists show reduced adverse effects as compared to μ-opioid receptor (MOP) agonists that are in the spotlight of the current "opioid crisis." Here, we report the first crystal structures of the DOP in an activated state, in complex with two relevant and structurally diverse agonists: the potent opioid agonist peptide KGCHM07 and the small-molecule agonist DPI-287 at 2.8 and 3.3 Å resolution, respectively. Our study identifies key determinants for agonist recognition, receptor activation, and DOP selectivity, revealing crucial differences between both agonist scaffolds. Our findings provide the first investigation into atomic-scale agonist binding at the DOP, supported by site-directed mutagenesis and pharmacological characterization. These structures will underpin the future structure-based development of DOP agonists for an improved pain treatment with fewer adverse effects.
PubMed: 31807708
DOI: 10.1126/sciadv.aax9115
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.3 Å)
Structure validation

229183

PDB entries from 2024-12-18

PDB statisticsPDBj update infoContact PDBjnumon