9pa5

(S)-ketamine bound mu-opioid receptor in complex with Gi1

spinqualitylabelsall models 9pa5, resolution 2.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9pa5 is a 5 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.92Å Ligands: JC9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GNAI1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division. Publication Abstract from PubMed Ketamine offers rapid relief for treatment-resistant depression and severe pain in the clinic, providing immediate benefits that traditional medications often fail to deliver. While its antagonistic action at the N-methyl-D-aspartate receptor (NMDAR) is a key mechanism, ketamine's dual nature as both a promising treatment and a drug with abuse potential suggests its therapeutic effects extend beyond NMDAR inhibition. Here we provide structural evidence of human opioid receptors bound to ketamine and its parent analog phencyclidine (PCP), supporting that both ligands can directly bind and activate opioid receptors. The structures, together with site-directed mutagenesis and structure-activity relationship studies, identify key motifs involved in ketamine and PCP recognition and efficacy modulation. Furthermore, we determine the structure of the ligand-free state of human kappa opioid receptor, revealing molecular details before ligand engagement. Compared to PCP, ketamine displays more notable binding dynamics in the orthosteric site that may contribute to its unique pharmacology at opioid receptors. Our findings highlight the importance of including opioid receptors to fully understand ketamine's versatility in clinical settings. Structural basis of opioid receptor activation by PCP and ketamine.,Jiang Q, Han J, Fine EJ, Ramos-Gonzalez N, Rangari VA, Ruiz MV, Critz ML, Suomivuori CM, Wang J, Albert TL, Whiddon K, Li K, Robertson MJ, Huang XP, Land BB, Majumdar S, Fay JF, Dror RO, Che T Nat Struct Mol Biol. 2026 Jun 22. doi: 10.1038/s41594-026-01839-y. PMID:42332075 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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