[English] 日本語
Yorodumi
- EMDB-14252: Bovine complex I in the presence of IM1761092, active class i (Co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-14252
TitleBovine complex I in the presence of IM1761092, active class i (Consensus)
Map dataConsensus map globally sharpened
Sample
  • Complex: NADH Ubiquinone oxidoreductase (Complex I)
Biological speciesBos taurus (cattle)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.44 Å
AuthorsBridges HR / Blaza JN / Yin Z / Chung I / Hirst J
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MC_U105663141 United Kingdom
Medical Research Council (MRC, United Kingdom)MC_UU_00015/2 United Kingdom
CitationJournal: Science / Year: 2023
Title: Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides.
Authors: Hannah R Bridges / James N Blaza / Zhan Yin / Injae Chung / Michael N Pollak / Judy Hirst /
Abstract: The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target ...The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides.
History
DepositionFeb 8, 2022-
Header (metadata) releaseFeb 8, 2023-
Map releaseFeb 8, 2023-
UpdateFeb 8, 2023-
Current statusFeb 8, 2023Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

Downloads & links

-
Map

FileDownload / File: emd_14252.map.gz / Format: CCP4 / Size: 1.1 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationConsensus map globally sharpened
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 660 pix.
= 482.46 Å
0.73 Å/pix.
x 660 pix.
= 482.46 Å
0.73 Å/pix.
x 660 pix.
= 482.46 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.731 Å
Density
Contour LevelBy AUTHOR: 0.018
Minimum - Maximum-0.050171867 - 0.11939942
Average (Standard dev.)-0.00012502314 (±0.003581205)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions660660660
Spacing660660660
CellA=B=C: 482.46 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_14252_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

-
Additional map: Consensus map locally sharpened

Fileemd_14252_additional_1.map
AnnotationConsensus map locally sharpened
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

-
Half map: Consensus halfmap2

Fileemd_14252_half_map_1.map
AnnotationConsensus halfmap2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

-
Half map: Consensus halfmap1

Fileemd_14252_half_map_2.map
AnnotationConsensus halfmap1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

-
Sample components

-
Entire : NADH Ubiquinone oxidoreductase (Complex I)

EntireName: NADH Ubiquinone oxidoreductase (Complex I)
Components
  • Complex: NADH Ubiquinone oxidoreductase (Complex I)

-
Supramolecule #1: NADH Ubiquinone oxidoreductase (Complex I)

SupramoleculeName: NADH Ubiquinone oxidoreductase (Complex I) / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#45
Source (natural)Organism: Bos taurus (cattle) / Organ: Heart
Molecular weightTheoretical: 1 MDa

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration3 mg/mL
BufferpH: 7.14
Component:
ConcentrationFormulaName
20.0 mMC4H11NO3Tris
50.0 mMNaClSodium chlorideSodium Chloride
0.05 %C24H46O11n-Dodecyl-B-D-Maltoside
GridModel: UltrAuFoil R0.6/1 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 90 sec. / Pretreatment - Atmosphere: AIR
Details: Grid also covalently modified by peg-thiol for 48 hours in a nitrogen atmosphere.
VitrificationCryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.44 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 48367
FSC plot (resolution estimation)

+
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