8f1c

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Current revision (07:04, 25 October 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8f1c is ON HOLD until Paper Publication
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==Voltage-gated potassium channel Kv3.1 with novel positive modulator (9M)-9-{5-chloro-6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-4-methylpyridin-3-yl}-2-methyl-7,9-dihydro-8H-purin-8-one (compound 4)==
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<StructureSection load='8f1c' size='340' side='right'caption='[[8f1c]], [[Resolution|resolution]] 2.92&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8f1c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8F1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F1C FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.92&#8491;</td></tr>
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<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=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</scene>, <scene name='pdbligand=X9T:(9M)-9-{5-chloro-6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-4-methylpyridin-3-yl}-2-methyl-7,9-dihydro-8H-purin-8-one'>X9T</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8f1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f1c OCA], [https://pdbe.org/8f1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f1c RCSB], [https://www.ebi.ac.uk/pdbsum/8f1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f1c ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/KCNC1_HUMAN KCNC1_HUMAN] Progressive myoclonic epilepsy type 7. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/KCNC1_HUMAN KCNC1_HUMAN] Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient (PubMed:25401298). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well. Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons.[UniProtKB:P25122]<ref>PMID:25401298</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K(+)) to diffuse across a hydrophobic cell membrane. These unique voltage-gated cation channels detect changes in membrane potential and, upon activation, help to return the depolarized cell to a resting state during the repolarization stage of each action potential. The Kv3 family of potassium channels is characterized by a high activation potential and rapid kinetics, which play a crucial role for the fast-spiking neuronal phenotype. Mutations in the Kv3.1 channel have been shown to have implications in various neurological diseases like epilepsy and Alzheimer's disease. Moreover, disruptions in neuronal circuitry involving Kv3.1 have been correlated with negative symptoms of schizophrenia. Here, we report the discovery of a novel positive modulator of Kv3.1, investigate its biophysical properties, and determine the cryo-EM structure of the compound in complex with Kv3.1. Structural analysis reveals the molecular determinants of positive modulation in Kv3.1 channels by this class of compounds and provides additional opportunities for rational drug design for the treatment of associated neurological disorders.
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Authors:
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Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels.,Chen YT, Hong MR, Zhang XJ, Kostas J, Li Y, Kraus RL, Santarelli VP, Wang D, Gomez-Llorente Y, Brooun A, Strickland C, Soisson SM, Klein DJ, Ginnetti AT, Marino MJ, Stachel SJ, Ishchenko A Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2220029120. doi: , 10.1073/pnas.2220029120. Epub 2023 Oct 9. PMID:37812700<ref>PMID:37812700</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8f1c" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Chen Y]]
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[[Category: Ishchenko A]]

Current revision

Voltage-gated potassium channel Kv3.1 with novel positive modulator (9M)-9-{5-chloro-6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-4-methylpyridin-3-yl}-2-methyl-7,9-dihydro-8H-purin-8-one (compound 4)

PDB ID 8f1c

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