4DKL

Crystal structure of the mu-opioid receptor bound to a morphinan antagonist

Summary for 4DKL

• Entry DOI: 10.2210/pdb4dkl/pdb
• Descriptor: Mu-type opioid receptor, lysozyme chimera, methyl 4-{[(5beta,6alpha)-17-(cyclopropylmethyl)-3,14-dihydroxy-4,5-epoxymorphinan-6-yl]amino}-4-oxobutanoate, SULFATE ION, ... (8 entities in total)
• Functional Keywords: g-protein coupled receptor, 7 transmembrane receptor, signaling protein-antagonist complex, signaling protein/antagonist
• Biological source: Mus musculus (mouse, bacteriophage T4); More
• Cellular location: Cell membrane ; Multi- pass membrane protein : P42866
• Total number of polymer chains: 1
• Total formula weight: 55761.67

Authors

Manglik, A.,Kruse, A.C.,Kobilka, T.S.,Thian, F.S.,Mathiesen, J.M.,Sunahara, R.K.,Pardo, L.,Weis, W.I.,Kobilka, B.K.,Granier, S. (deposition date: 2012-02-03, release date: 2012-03-21, Last modification date: 2023-09-13)

Primary citation

Manglik, A.,Kruse, A.C.,Kobilka, T.S.,Thian, F.S.,Mathiesen, J.M.,Sunahara, R.K.,Pardo, L.,Weis, W.I.,Kobilka, B.K.,Granier, S.
Crystal structure of the {mu}-opioid receptor bound to a morphinan antagonist.
Nature, 485:321-326, 2012

PubMed Abstract: Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled µ-opioid receptor (µ-OR) in the central nervous system. Here we describe the 2.8 Å crystal structure of the mouse µ-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the µ-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.

PubMed: 22437502
DOI: 10.1038/nature10954

Experimental method

X-RAY DIFFRACTION (2.8 Å)