[English] 日本語
Yorodumi
- PDB-8f1c: Voltage-gated potassium channel Kv3.1 with novel positive modulat... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8f1c
TitleVoltage-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)
ComponentsPotassium voltage-gated channel subfamily C member 1
KeywordsTRANSPORT PROTEIN / ion channel / positive modulator / voltage gated / voltage gated potassium channel
Function / homology
Function and homology information


response to nerve growth factor / globus pallidus development / response to light intensity / response to auditory stimulus / response to potassium ion / response to fibroblast growth factor / delayed rectifier potassium channel activity / corpus callosum development / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport ...response to nerve growth factor / globus pallidus development / response to light intensity / response to auditory stimulus / response to potassium ion / response to fibroblast growth factor / delayed rectifier potassium channel activity / corpus callosum development / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / optic nerve development / neuronal cell body membrane / response to amine / voltage-gated potassium channel activity / calyx of Held / kinesin binding / axolemma / voltage-gated potassium channel complex / axon terminus / potassium ion transmembrane transport / dendrite membrane / cerebellum development / protein tetramerization / protein homooligomerization / potassium ion transport / response to toxic substance / cellular response to xenobiotic stimulus / presynaptic membrane / postsynaptic membrane / transmembrane transporter binding / cell surface / plasma membrane
Similarity search - Function
Potassium channel, voltage dependent, Kv3.1 / Potassium channel, voltage dependent, Kv3 / Potassium channel, voltage dependent, Kv / Potassium channel tetramerisation-type BTB domain / BTB/POZ domain / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / Voltage-dependent channel domain superfamily / SKP1/BTB/POZ domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
: / Chem-POV / Chem-X9T / Potassium voltage-gated channel subfamily C member 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.92 Å
AuthorsChen, Y. / Ishchenko, A.
Funding support United States, 1items
OrganizationGrant numberCountry
Merck & Co. United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2023
Title: Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels.
Authors: Yun-Ting Chen / Mee Ra Hong / Xin-Jun Zhang / James Kostas / Yuxing Li / Richard L Kraus / Vincent P Santarelli / Deping Wang / Yacob Gomez-Llorente / Alexei Brooun / Corey Strickland / ...Authors: Yun-Ting Chen / Mee Ra Hong / Xin-Jun Zhang / James Kostas / Yuxing Li / Richard L Kraus / Vincent P Santarelli / Deping Wang / Yacob Gomez-Llorente / Alexei Brooun / Corey Strickland / Stephen M Soisson / Daniel J Klein / Anthony T Ginnetti / Michael J Marino / Shawn J Stachel / Andrii Ishchenko /
Abstract: 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 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.
History
DepositionNov 4, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 25, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Potassium voltage-gated channel subfamily C member 1
B: Potassium voltage-gated channel subfamily C member 1
C: Potassium voltage-gated channel subfamily C member 1
D: Potassium voltage-gated channel subfamily C member 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)256,19120
Polymers250,9814
Non-polymers5,21016
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein
Potassium voltage-gated channel subfamily C member 1 / NGK2 / Voltage-gated potassium channel subunit Kv3.1 / Voltage-gated potassium channel subunit Kv4


Mass: 62745.266 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KCNC1 / Cell line (production host): Expi293, human-derived / Production host: Homo sapiens (human) / References: UniProt: P48547
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
#3: Chemical
ChemComp-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


Mass: 437.879 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C22H20ClN5O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-POV / (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / POPC / POPC


Mass: 760.076 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C42H82NO8P / Comment: phospholipid*YM
#5: Chemical
ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: K
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: potassium voltage-gated channelVoltage-gated potassium channel
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.24 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human) / Cell: Expi293, human-derived / Plasmid: Mammalian expression vector EGFP-MCS-pcDNA3.1
Buffer solutionpH: 8
SpecimenConc.: 3.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 42.5 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.20.1_4487: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1883143
3D reconstructionResolution: 2.92 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 125905 / Symmetry type: POINT
Atomic model buildingProtocol: AB INITIO MODEL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00313320
ELECTRON MICROSCOPYf_angle_d0.44318136
ELECTRON MICROSCOPYf_dihedral_angle_d9.8694704
ELECTRON MICROSCOPYf_chiral_restr0.0361964
ELECTRON MICROSCOPYf_plane_restr0.0042248

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more