6e59

Crystal structure of the human NK1 tachykinin receptor

spinqualitylabelsall models 6e59, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6e59 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 3.4Å Ligands: L76 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9V2J8_PYRAB NK1R_HUMAN This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K. Publication Abstract from PubMed The NK1 tachykinin G-protein-coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK1R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK1R (hNK1R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK1R are inhibitors for chemotherapy-induced nausea and vomiting (CINV). To better understand the molecular basis of ligand recognition and selectivity, we solved the crystal structure of hNK1R bound to the inhibitor L760735, a close analog of the drug aprepitant. Our crystal structure reveals the basis for antagonist interaction in the deep and narrow orthosteric pocket of the receptor. We used our structure as a template for computational docking and molecular-dynamics simulations to dissect the energetic importance of binding pocket interactions and model the binding of aprepitant. The structure of hNK1R is a valuable tool in the further development of tachykinin receptor modulators for multiple clinical applications. Crystal structure of the human NK1 tachykinin receptor.,Yin J, Chapman K, Clark LD, Shao Z, Borek D, Xu Q, Wang J, Rosenbaum DM Proc Natl Acad Sci U S A. 2018 Dec 11. pii: 1812717115. doi:, 10.1073/pnas.1812717115. PMID:30538204 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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