5ws3

Crystal structures of human orexin 2 receptor bound to the selective antagonist EMPA determined by serial femtosecond crystallography at SACLA

spinqualitylabelsall models 5ws3, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ws3 is a 1 chain structure with sequence from Homo sapiens and Pyrococcus abyssi GE5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: 1PE, 7MA, OLA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9V2J8_PYRAB OX2R_HUMAN Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides. Publication Abstract from PubMed Orexin peptides in the brain regulate physiological functions such as the sleep-wake cycle, and are thus drug targets for the treatment of insomnia. Using serial femtosecond crystallography and multi-crystal data collection with a synchrotron light source, we determined structures of human orexin 2 receptor in complex with the subtype-selective antagonist EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylme thyl-acetamide) at 2.30-A and 1.96-A resolution. In comparison with the non-subtype-selective antagonist suvorexant, EMPA contacted fewer residues through hydrogen bonds at the orthosteric site, explaining the faster dissociation rate. Comparisons among these OX2R structures in complex with selective antagonists and previously determined OX1R/OX2R structures bound to non-selective antagonists revealed that the residue at positions 2.61 and 3.33 were critical for the antagonist selectivity in OX2R. The importance of these residues for binding selectivity to OX2R was also revealed by molecular dynamics simulation. These results should facilitate the development of antagonists for orexin receptors. Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective Antagonist EMPA.,Suno R, Kimura KT, Nakane T, Yamashita K, Wang J, Fujiwara T, Yamanaka Y, Im D, Horita S, Tsujimoto H, Tawaramoto MS, Hirokawa T, Nango E, Tono K, Kameshima T, Hatsui T, Joti Y, Yabashi M, Shimamoto K, Yamamoto M, Rosenbaum DM, Iwata S, Shimamura T, Kobayashi T Structure. 2017 Nov 27. pii: S0969-2126(17)30358-1. doi:, 10.1016/j.str.2017.11.005. PMID:29225076 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Orexin and Orexin receptor

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