8fz7
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==TpeA bound closed MthK-A88F mutant in nanodisc== | |
| + | <StructureSection load='8fz7' size='340' side='right'caption='[[8fz7]], [[Resolution|resolution]] 2.88Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8fz7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FZ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FZ7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.88Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PGW:(1R)-2-{[(S)-{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(HEXADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>PGW</scene>, <scene name='pdbligand=YQ1:1-(tripentyl-$l^{4}-azanyl)pentane'>YQ1</scene></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=8fz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fz7 OCA], [https://pdbe.org/8fz7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fz7 RCSB], [https://www.ebi.ac.uk/pdbsum/8fz7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fz7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MTHK_METTH MTHK_METTH] Calcium-gated potassium channel. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Quaternary ammonium blockers were previously shown to bind in the pore to block both open and closed conformations of large-conductance calcium-activated potassium (BK and MthK) channels. Because blocker entry was assumed through the intracellular entryway (bundle crossing), closed-pore access suggested that the gate was not at the bundle crossing. Structures of closed MthK, a Methanobacterium thermoautotrophicum homolog of BK channels, revealed a tightly constricted intracellular gate, leading us to investigate the membrane-facing fenestrations as alternative pathways for blocker access directly from the membrane. Atomistic free energy simulations showed that intracellular blockers indeed access the pore through the fenestrations, and a mutant channel with narrower fenestrations displayed no closed-state TPeA block at concentrations that blocked the wild-type channel. Apo BK channels display similar fenestrations, suggesting that blockers may use them as access paths into closed channels. Thus, membrane fenestrations represent a non-canonical pathway for selective targeting of specific channel conformations, opening novel ways to selectively drug BK channels. | ||
| - | + | Calcium-gated potassium channel blockade via membrane-facing fenestrations.,Fan C, Flood E, Sukomon N, Agarwal S, Allen TW, Nimigean CM Nat Chem Biol. 2023 Aug 31. doi: 10.1038/s41589-023-01406-2. PMID:37653172<ref>PMID:37653172</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8fz7" style="background-color:#fffaf0;"></div> |
| - | [[Category: Agarwal | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Methanothermobacter thermautotrophicus]] | ||
| + | [[Category: Agarwal S]] | ||
| + | [[Category: Nimigean CM]] | ||
Current revision
TpeA bound closed MthK-A88F mutant in nanodisc
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