6pza | pdb_00006pza

Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP and glibenclamide

spinqualitylabelsall models 6pza, resolution 3.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6pza is a 2 chain structure with sequence from Black-bellied hamster and Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, GBM Related: 6pzb, 6pz9, 6pzi, 6pzc Gene: ABCC8, SUR (Black-bellied hamster), Kcnj11 (Buffalo rat) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ABCC8_CRICR] Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive potassium channels and insulin release.[UniProtKB:Q09428] [KCJ11_RAT] This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity). Publication Abstract from PubMed ATP-sensitive potassium (KATP) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic beta-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse KATP inhibitors are known to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of a mammalian KATP channel bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. We found all three drugs bind within a common pocket in SUR1. Further, we found the N-terminus of Kir6.2 inserted within the central cavity of the SUR1 ABC core, adjacent the drug binding pocket. The findings reveal a common mechanism by which diverse compounds stabilize the Kir6.2 N-terminus within SUR1's ABC core, allowing it to act as a firm 'handle' for the assembly of metastable mutant SUR1-Kir6.2 complexes. Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM.,Martin GM, Sung MW, Yang Z, Innes LM, Kandasamy B, David LL, Yoshioka C, Shyng SL Elife. 2019 Jul 25;8. pii: 46417. doi: 10.7554/eLife.46417. PMID:31343405 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Potassium channel 3D structures

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