7jpx

Rabbit Cav1.1 in the presence of 100 micromolar amlodipine in nanodiscs at 2.9 Angstrom resolution

spinqualitylabelsall models 7jpx, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7jpx is a 3 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.9Å Ligands: 3PE, 6UB, CA, PC1, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 1,4-Dihydropyridines (DHP), the most commonly used antihypertensives, function by inhibiting the L-type voltage-gated Ca(2+) (Ca(v) ) channels. DHP compounds exhibit chirality-specific antagonistic or agonistic effects. The structure of rabbit Ca(v) 1.1 bound to an achiral drug nifedipine reveals the general binding mode for DHP drugs, but the molecular basis for chiral specificity remained elusive. Herein, we report five cryo-EM structures of nanodisc-embedded Ca(v) 1.1 in the presence of the bestselling drug amlodipine, a DHP antagonist (R)-(+)-Bay K8644, and a titration of its agonistic enantiomer (S)-(-)-Bay K8644 at resolutions of 2.9-3.4 A. The amlodipine-bound structure reveals the molecular basis for the high efficacy of the drug. All structures with the addition of the Bay K8644 enantiomers exhibit similar inactivated conformations, suggesting that (S)-(-)-Bay K8644, when acting as an agonist, is insufficient to lock the activated state of the channel for a prolonged duration. Structural Basis of the Modulation of the Voltage-Gated Calcium Ion Channel Ca(v) 1.1 by Dihydropyridine Compounds*.,Gao S, Yan N Angew Chem Int Ed Engl. 2021 Feb 8;60(6):3131-3137. doi: 10.1002/anie.202011793. , Epub 2020 Dec 10. PMID:33125829 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ion channels 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA