2yme

Crystal structure of a mutant binding protein (5HTBP-AChBP) in complex with granisetron

spinqualitylabelsall models 2yme, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yme is a 10 chain structure with sequence from Aplysia californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CWB, NA, NAG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8WSF8_APLCA Publication Abstract from PubMed The 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation-pi interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. Structural basis of ligand recognition in 5-HT3 receptors.,Kesters D, Thompson AJ, Brams M, van Elk R, Spurny R, Geitmann M, Villalgordo JM, Guskov A, Helena Danielson U, Lummis SC, Smit AB, Ulens C EMBO Rep. 2012 Nov 30. doi: 10.1038/embor.2012.189. PMID:23196367 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholine binding protein 3D structures

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