[English] 日本語
Yorodumi
- EMDB-61642: Cryo-EM structure of human BKca channel-compound 10b complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-61642
TitleCryo-EM structure of human BKca channel-compound 10b complex
Map data
Sample
  • Complex: BKca channel-compound 10b complex
    • Protein or peptide: Calcium-activated potassium channel subunit alpha-1
  • Ligand: MAGNESIUM ION
  • Ligand: CALCIUM ION
  • Ligand: POTASSIUM ION
  • Ligand: 5-azanyl-2-[2,3,5,6-tetrakis(fluoranyl)-4-(trifluoromethyl)phenoxy]phenol
  • Ligand: CHOLESTEROL HEMISUCCINATE
KeywordsBKca channel / compound 10b / Cryo-EM / MEMBRANE PROTEIN
Function / homology
Function and homology information


Acetylcholine inhibits contraction of outer hair cells / Ca2+ activated K+ channels / micturition / response to carbon monoxide / large conductance calcium-activated potassium channel activity / calcium-activated potassium channel activity / negative regulation of cell volume / smooth muscle contraction involved in micturition / intracellular potassium ion homeostasis / Sensory processing of sound by inner hair cells of the cochlea ...Acetylcholine inhibits contraction of outer hair cells / Ca2+ activated K+ channels / micturition / response to carbon monoxide / large conductance calcium-activated potassium channel activity / calcium-activated potassium channel activity / negative regulation of cell volume / smooth muscle contraction involved in micturition / intracellular potassium ion homeostasis / Sensory processing of sound by inner hair cells of the cochlea / response to osmotic stress / cGMP effects / voltage-gated potassium channel activity / voltage-gated potassium channel complex / potassium ion transmembrane transport / regulation of membrane potential / potassium ion transport / caveola / response to calcium ion / vasodilation / actin binding / postsynaptic membrane / response to hypoxia / apical plasma membrane / positive regulation of apoptotic process / metal ion binding / identical protein binding / membrane / plasma membrane
Similarity search - Function
: / Ca2+-activated K+ channel Slowpoke, TrkA_C like domain / Calcium-activated potassium channel BK, alpha subunit / : / : / Calcium-activated BK potassium channel alpha subunit / Calcium-activated potassium channel slowpoke-like RCK domain / RCK N-terminal domain profile. / Ion transport domain / Ion transport protein / NAD(P)-binding domain superfamily
Similarity search - Domain/homology
Calcium-activated potassium channel subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsKim S / Park S / Lee NY / Lee EY / Lee N / Roh EC / Kim YG / Kim HJ / Jin MS / Park CS / Kim YC
Funding support Korea, Republic Of, 2 items
OrganizationGrant numberCountry
Other governmentRS-2023-00258812 Korea, Republic Of
National Research Foundation (NRF, Korea)RS-2024-00411137 Korea, Republic Of
CitationJournal: J Med Chem / Year: 2025
Title: Discovery of Diphenyl Ether Derivatives as Novel BK Channel Activators: Structure-Activity Relationship, Cryo-EM Complex Structures, and Animal Studies.
Authors: Soo Bin Park / Na Young Lee / Eun-Young Lee / Subin Kim / Narasaem Lee / Eun Chae Roh / Yoon Gyoon Kim / Hee Jin Kim / Mi Sun Jin / Chul-Seung Park / Yong-Chul Kim /
Abstract: The BK channel, a large-conductance calcium-activated potassium channel, plays a crucial role in maintaining the homeostasis of the micturition cycle and airway-related functions. In this study, we ...The BK channel, a large-conductance calcium-activated potassium channel, plays a crucial role in maintaining the homeostasis of the micturition cycle and airway-related functions. In this study, we optimized a novel BK channel activator, , with a diphenyl ether structure identified from library screening. This led to the discovery of potent activators, (EC = 0.12 μM, cell-based assay) and , an orally bioavailable derivative. Compound demonstrated potent efficacy in a spontaneous hypertensive rat (SHR) of urinary incontinence model, while compound showed dose-dependent cough suppression efficacy with an ED of 11.8 mg/kg in a citric acid-induced cough model. Furthermore, we reported the cryo-electron microscopy (cryo-EM) structures of the BK channel in complex with and at resolutions of 2.8 and 3.4 Å. Based on structural analyses, we determined the binding sites and key interaction residues of , which were validated via mutation studies.
History
DepositionSep 24, 2024-
Header (metadata) releaseFeb 26, 2025-
Map releaseFeb 26, 2025-
UpdateMar 12, 2025-
Current statusMar 12, 2025Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_61642.png

Downloads & links

-
Map

FileDownload / File: emd_61642.map.gz / Format: CCP4 / Size: 59.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 250 pix.
= 270. Å		1.08 Å/pix.
x 250 pix.
= 270. Å		1.08 Å/pix.
x 250 pix.
= 270. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.08 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.172
Minimum - Maximum-0.20701848 - 0.6672611
Average (Standard dev.)0.013641136 (±0.0391915)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions250250250
Spacing250250250
CellA=B=C: 270.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_61642_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_61642_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : BKca channel-compound 10b complex

EntireName: BKca channel-compound 10b complex
Components
  • Complex: BKca channel-compound 10b complex
    • Protein or peptide: Calcium-activated potassium channel subunit alpha-1
  • Ligand: MAGNESIUM ION
  • Ligand: CALCIUM ION
  • Ligand: POTASSIUM ION
  • Ligand: 5-azanyl-2-[2,3,5,6-tetrakis(fluoranyl)-4-(trifluoromethyl)phenoxy]phenol
  • Ligand: CHOLESTEROL HEMISUCCINATE

-
Supramolecule #1: BKca channel-compound 10b complex

SupramoleculeName: BKca channel-compound 10b complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Calcium-activated potassium channel subunit alpha-1

MacromoleculeName: Calcium-activated potassium channel subunit alpha-1 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 126.049961 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDALIIPVTM EVPCDSRGQR MWWAFLASSM VTFFGGLFII LLWRTLKYLW TVCCHCGGKT KEAQKINNGS SQADGTLKPV DEKEEAVAA EVGWMTSVKD WAGVMISAQT LTGRVLVVLV FALSIGALVI YFIDSSNPIE SCQNFYKDFT LQIDMAFNVF F LLYFGLRF ...String:
MDALIIPVTM EVPCDSRGQR MWWAFLASSM VTFFGGLFII LLWRTLKYLW TVCCHCGGKT KEAQKINNGS SQADGTLKPV DEKEEAVAA EVGWMTSVKD WAGVMISAQT LTGRVLVVLV FALSIGALVI YFIDSSNPIE SCQNFYKDFT LQIDMAFNVF F LLYFGLRF IAANDKLWFW LEVNSVVDFF TVPPVFVSVY LNRSWLGLRF LRALRLIQFS EILQFLNILK TSNSIKLVNL LS IFISTWL TAAGFIHLVE NSGDPWENFQ NNQALTYWEC VYLLMVTMST VGYGDVYAKT TLGRLFMVFF ILGGLAMFAS YVP EIIELI GNRKKYGGSY SAVSGRKHIV VCGHITLESV SNFLKDFLHK DRDDVNVEIV FLHNISPNLE LEALFKRHFT QVEF YQGSV LNPHDLARVK IESADACLIL ANKYCADPDA EDASNIMRVI SIKNYHPKIR IITQMLQYHN KAHLLNIPSW NWKEG DDAI CLAELKLGFI AQSCLAQGLS TMLANLFSMR SFIKIEEDTW QKYYLEGVSN EMYTEYLSSA FVGLSFPTVC ELCFVK LKL LMIAIEYKSA NRESRILINP GNHLKIQEGT LGFFIASDAK EVKRAFFYCK ACHDDITDPK RIKKCGCKRP KMSIYKR MR RACCFDCGRS ERDCSCMSGR VRGNVDTLER AFPLSSVSVN DCSTSFRAFE DEQPSTLSPK KKQRNGGMRN SPNTSPKL M RHDPLLIPGN DQIDNMDSNV KKYDSTGMFH WCAPKEIEKV ILTRSEAAMT VLSGHVVVCI FGDVSSALIG LRNLVMPLR ASNFHYHELK HIVFVGSIEY LKREWETLHN FPKVSILPGT PLSRADLRAV NINLCDMCVI LSANQNNIDD TSLQDKECIL ASLNIKSMQ FDDSIGVLQA NSQGFTPPGM DRSSPDNSPV HGMLRQPSIT TGVNIPIITE LVNDTNVQFL DQDDDDDPDT E LYLTQPFA CGTAFAVSVL DSLMSATYFN DNILTLIRTL VTGGATPELE ALIAEENALR GGYSTPQTLA NRDRCRVAQL AL LDGPFAD LGDGGCYGDL FCKALKTYNM LCFGIYRLRD AHLSTPSQCT KRYVITNPPY EFELVPTDLI FCLMQFDHNA GQ

UniProtKB: Calcium-activated potassium channel subunit alpha-1

-
Macromolecule #2: MAGNESIUM ION

MacromoleculeName: MAGNESIUM ION / type: ligand / ID: 2 / Number of copies: 4 / Formula: MG
Molecular weightTheoretical: 24.305 Da

-
Macromolecule #3: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 8 / Formula: CA
Molecular weightTheoretical: 40.078 Da

-
Macromolecule #4: POTASSIUM ION

MacromoleculeName: POTASSIUM ION / type: ligand / ID: 4 / Number of copies: 3 / Formula: K
Molecular weightTheoretical: 39.098 Da

-
Macromolecule #5: 5-azanyl-2-[2,3,5,6-tetrakis(fluoranyl)-4-(trifluoromethyl)phenox...

MacromoleculeName: 5-azanyl-2-[2,3,5,6-tetrakis(fluoranyl)-4-(trifluoromethyl)phenoxy]phenol
type: ligand / ID: 5 / Number of copies: 4 / Formula: A1L4E
Molecular weightTheoretical: 341.181 Da

-
Macromolecule #6: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 6 / Number of copies: 16 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 59.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 0.7000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 414785
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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