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| | <SX load='6pzc' size='340' side='right' viewer='molstar' caption='[[6pzc]], [[Resolution|resolution]] 4.34Å' scene=''> | | <SX load='6pzc' size='340' side='right' viewer='molstar' caption='[[6pzc]], [[Resolution|resolution]] 4.34Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pzc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Black-bellied_hamster Black-bellied hamster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PZC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PZC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pzc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetus_cricetus Cricetus cricetus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PZC FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABCC8, SUR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10034 Black-bellied hamster])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.34Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pzc OCA], [http://pdbe.org/6pzc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pzc RCSB], [http://www.ebi.ac.uk/pdbsum/6pzc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pzc ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6pzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pzc OCA], [https://pdbe.org/6pzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pzc RCSB], [https://www.ebi.ac.uk/pdbsum/6pzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pzc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ABCC8_CRICR ABCC8_CRICR]] Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive potassium channels and insulin release.[UniProtKB:Q09428] | + | [https://www.uniprot.org/uniprot/ABCC8_CRICR ABCC8_CRICR] Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive potassium channels and insulin release.[UniProtKB:Q09428] |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == 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<ref>PMID:31343405</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6pzc" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Black-bellied hamster]] | + | [[Category: Cricetus cricetus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Martin, G M]] | + | [[Category: Martin GM]] |
| - | [[Category: Shyng, S L]] | + | [[Category: Shyng SL]] |
| - | [[Category: Sung, M W]] | + | [[Category: Sung MW]] |
| - | [[Category: Yoshioka, C]] | + | [[Category: Yoshioka C]] |
| - | [[Category: Carbamazepine]]
| + | |
| - | [[Category: Katp]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Sur1]]
| + | |
