4EJ4: Structure Of The Delta Opioid Receptor Bound To Naltrindole

Citation:
Abstract
The opioid receptor family comprises three members, the micro-, delta- and kappa-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The delta-opioid receptor (delta-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the micro-OR and kappa-OR have recently been solved. Here we report the crystal structure of the mouse delta-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the micro-OR and kappa-OR, the delta-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the delta-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.
PDB ID: 4EJ4Download
MMDB ID: 99756
PDB Deposition Date: 2012/4/6
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 3.4  Å
Similar Structures:
Biological Unit for 4EJ4: monomeric; determined by author and by software (PISA)
Molecular Components in 4EJ4
Label Count Molecule
Protein (1 molecule)
1
Delta-type Opioid Receptor, Lysozyme Chimera
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.