View source for 5bkk


==bbTBA-bound closed MthK channel in nanodisc==
<StructureSection load='5bkk' size='340' side='right'caption='[[5bkk]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5bkk]] 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=5BKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BKK 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]] 3.5&#8491;</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=YQ4:(~{R})-phenyl-[4-[(tributyl-$l^{4}-azanyl)methyl]phenyl]methanol'>YQ4</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=5bkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bkk OCA], [https://pdbe.org/5bkk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bkk RCSB], [https://www.ebi.ac.uk/pdbsum/5bkk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bkk 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. 2024 Jan;20(1):52-61. doi: 10.1038/s41589-023-01406-2. Epub 2023 , Aug 31. PMID:37653172<ref>PMID:37653172</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5bkk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Methanothermobacter thermautotrophicus]]
[[Category: Fan C]]
[[Category: Nimigean CM]]