6lqa

voltage-gated sodium channel Nav1.5 with quinidinevoltage-gated sodium channel Nav1.5 with quinidine

Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.3Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Na v 1.5, the primary voltage-gated Na + (Na v ) channel in heart, is a major target for class I antiarrhythmic agents. Here we present the cryo-EM structure of full-length human Na v 1.5 bound to quinidine, a class Ia antiarrhythmic drug, at 3.3 A resolution. Quinidine is positioned right beneath the selectivity filter in the pore domain and coordinated by residues from repeats I, III, and IV. Pore blockade by quinidine is achieved through both direct obstruction of the ion permeation path and induced rotation of an invariant Tyr residue that tightens the intracellular gate. Structural comparison with a truncated rat Na v 1.5 in the presence of flecainide, a class Ic agent, reveals distinct binding poses for the two antiarrhythmics within the pore domain. Our work reported here, along with previous studies, reveals the molecular basis for the mechanism of action of class I antiarrhythmic drugs. Structural Basis for Pore Blockade of the Human Cardiac Sodium Channel Nav1.5 by the Antiarrhythmic Drug Quinidine.,Li Z, Jin X, Wu T, Huang G, Wu K, Lei J, Pan X, Yan N Angew Chem Int Ed Engl. 2021 Mar 8. doi: 10.1002/anie.202102196. PMID:33684260 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

spinqualitylabelsall models 6lqa, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image