6w1j

Cryo-EM structure of 5HT3A receptor in presence of Alosetron

spinqualitylabelsall models 6w1j, resolution 2.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.92Å Ligands: BMA, CL, NAG, S7Y Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Serotonin receptors (5-HT3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HT3AR in complex with palonosetron, ondansetron, and alosetron. Molecular dynamic simulations of these structures embedded in a fully-hydrated lipid environment assessed the stability of ligand-binding poses and drug-target interactions over time. Together with simulation results of apo- and serotonin-bound 5-HT3AR, the study reveals a distinct interaction fingerprint between the various setrons and binding-pocket residues that may underlie their diverse affinities. In addition, varying degrees of conformational change in the setron-5-HT3AR structures, throughout the channel and particularly along the channel activation pathway, suggests a novel mechanism of competitive inhibition. High-resolution structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition.,Basak S, Kumar A, Ramsey S, Gibbs E, Kapoor A, Filizola M, Chakrapani S Elife. 2020 Oct 16;9. pii: 57870. doi: 10.7554/eLife.57870. PMID:33063666 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 5-hydroxytryptamine receptor 3D structures

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