4DKL

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

4DKL の概要

• エントリーDOI: 10.2210/pdb4dkl/pdb
• 分子名称: 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)
• 機能のキーワード: g-protein coupled receptor, 7 transmembrane receptor, signaling protein-antagonist complex, signaling protein/antagonist
• 由来する生物種: Mus musculus (mouse, bacteriophage T4); 詳細
• 細胞内の位置: Cell membrane ; Multi- pass membrane protein : P42866
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55761.67

構造登録者

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. (登録日: 2012-02-03, 公開日: 2012-03-21, 最終更新日: 2024-11-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)