[English] 日本語
Yorodumi
- PDB-8g0c: Cryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP s... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8g0c
TitleCryo-EM structure of TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 1 (backbone model)
Components(ATP synthase ...) x 8
KeywordsTRANSLOCASE/INHIBITOR / ATP synthase / mycobacterial / inhibitor / tuberculosis / antibiotic / HYDROLASE / TRANSLOCASE-INHIBITOR complex
Function / homology
Function and homology information


proton motive force-driven plasma membrane ATP synthesis / proton-transporting ATP synthase complex, coupling factor F(o) / proton-transporting ATP synthase complex, catalytic core F(1) / H+-transporting two-sector ATPase / proton-transporting ATPase activity, rotational mechanism / proton-transporting ATP synthase activity, rotational mechanism / hydrolase activity / lipid binding / ATP hydrolysis activity / ATP binding / plasma membrane
Similarity search - Function
ATP synthase, F0 complex, subunit b, bacterial / F-type ATP synthase subunit B-like, membrane domain superfamily / ATP synthase, F0 complex, subunit A, bacterial/chloroplast / ATP synthase, F0 complex, subunit b/b', bacterial/chloroplast / ATP synthase B/B' CF(0) / ATP synthase, F0 complex, subunit C, bacterial/chloroplast / ATP synthase, F0 complex, subunit A / ATP synthase, F0 complex, subunit A, active site / ATP synthase, F0 complex, subunit A superfamily / ATP synthase A chain ...ATP synthase, F0 complex, subunit b, bacterial / F-type ATP synthase subunit B-like, membrane domain superfamily / ATP synthase, F0 complex, subunit A, bacterial/chloroplast / ATP synthase, F0 complex, subunit b/b', bacterial/chloroplast / ATP synthase B/B' CF(0) / ATP synthase, F0 complex, subunit C, bacterial/chloroplast / ATP synthase, F0 complex, subunit A / ATP synthase, F0 complex, subunit A, active site / ATP synthase, F0 complex, subunit A superfamily / ATP synthase A chain / ATP synthase a subunit signature. / ATPase, OSCP/delta subunit / ATP synthase delta (OSCP) subunit / ATP synthase, F1 complex, delta/epsilon subunit / ATP synthase, F1 complex, delta/epsilon subunit, N-terminal / F0F1 ATP synthase delta/epsilon subunit, N-terminal / ATP synthase, Delta/Epsilon chain, beta-sandwich domain / ATP synthase, F0 complex, subunit C / F1F0 ATP synthase subunit C superfamily / ATP synthase, F0 complex, subunit C, DCCD-binding site / ATP synthase c subunit signature. / ATP synthase, F1 complex, gamma subunit conserved site / ATP synthase gamma subunit signature. / ATP synthase, F1 complex, beta subunit / ATP synthase, alpha subunit, C-terminal domain superfamily / ATP synthase, F1 complex, gamma subunit / ATP synthase, F1 complex, gamma subunit superfamily / ATP synthase / ATP synthase, alpha subunit, C-terminal / ATP synthase, F1 complex, alpha subunit / ATP synthase, F1 complex, alpha subunit nucleotide-binding domain / ATP synthase alpha/beta chain, C terminal domain / V-ATPase proteolipid subunit C-like domain / F/V-ATP synthase subunit C superfamily / ATP synthase subunit C / ATPase, F1/V1 complex, beta/alpha subunit, C-terminal / ATP synthase subunit alpha, N-terminal domain-like superfamily / ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain superfamily / ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain / ATP synthase alpha/beta family, beta-barrel domain / ATPase, alpha/beta subunit, nucleotide-binding domain, active site / ATP synthase alpha and beta subunits signature. / ATPase, F1/V1/A1 complex, alpha/beta subunit, nucleotide-binding domain / ATP synthase alpha/beta family, nucleotide-binding domain / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-TRIPHOSPHATE / PHOSPHATE ION / Chem-YGR / ATP synthase epsilon chain / ATP synthase subunit beta / ATP synthase gamma chain / ATP synthase subunit alpha / ATP synthase subunit b-delta / ATP synthase subunit b / ATP synthase subunit c / ATP synthase subunit a
Similarity search - Component
Biological speciesMycolicibacterium smegmatis MC2 155 (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsCourbon, G.M. / Rubinstein, J.L.
Funding support Canada, 1items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR)PJT162186 Canada
CitationJournal: EMBO J / Year: 2023
Title: Mechanism of mycobacterial ATP synthase inhibition by squaramides and second generation diarylquinolines.
Authors: Gautier M Courbon / Paul R Palme / Lea Mann / Adrian Richter / Peter Imming / John L Rubinstein /
Abstract: Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase ...Mycobacteria, such as Mycobacterium tuberculosis, depend on the activity of adenosine triphosphate (ATP) synthase for growth. The diarylquinoline bedaquiline (BDQ), a mycobacterial ATP synthase inhibitor, is an important medication for treatment of drug-resistant tuberculosis but suffers from off-target effects and is susceptible to resistance mutations. Consequently, both new and improved mycobacterial ATP synthase inhibitors are needed. We used electron cryomicroscopy and biochemical assays to study the interaction of Mycobacterium smegmatis ATP synthase with the second generation diarylquinoline TBAJ-876 and the squaramide inhibitor SQ31f. The aryl groups of TBAJ-876 improve binding compared with BDQ, while SQ31f, which blocks ATP synthesis ~10 times more potently than ATP hydrolysis, binds a previously unknown site in the enzyme's proton-conducting channel. Remarkably, BDQ, TBAJ-876, and SQ31f all induce similar conformational changes in ATP synthase, suggesting that the resulting conformation is particularly suited for drug binding. Further, high concentrations of the diarylquinolines uncouple the transmembrane proton motive force while for SQ31f they do not, which may explain why high concentrations of diarylquinolines, but not SQ31f, have been reported to kill mycobacteria.
History
DepositionJan 31, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 15, 2023Provider: repository / Type: Initial release
Revision 1.1Jul 12, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Aug 9, 2023Group: Database references / Category: citation / Item: _citation.journal_volume

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: ATP synthase subunit alpha
C: ATP synthase subunit alpha
A: ATP synthase subunit alpha
E: ATP synthase subunit beta
F: ATP synthase subunit beta
D: ATP synthase subunit beta
G: ATP synthase gamma chain
H: ATP synthase epsilon chain
b: ATP synthase subunit b
d: ATP synthase subunit b-delta
6: ATP synthase subunit c
7: ATP synthase subunit c
8: ATP synthase subunit c
9: ATP synthase subunit c
1: ATP synthase subunit c
2: ATP synthase subunit c
3: ATP synthase subunit c
4: ATP synthase subunit c
5: ATP synthase subunit c
a: ATP synthase subunit a
hetero molecules


Theoretical massNumber of molelcules
Total (without water)555,49936
Polymers548,67520
Non-polymers6,82416
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
ATP synthase ... , 8 types, 20 molecules BCAEFDGHbd678912345a

#1: Protein ATP synthase subunit alpha / / ATP synthase F1 sector subunit alpha / F-ATPase subunit alpha


Mass: 58951.461 Da / Num. of mol.: 3 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R202, H+-transporting two-sector ATPase
#2: Protein ATP synthase subunit beta / / ATP synthase F1 sector subunit beta / F-ATPase subunit beta


Mass: 51670.453 Da / Num. of mol.: 3 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R200, H+-transporting two-sector ATPase
#3: Protein ATP synthase gamma chain / ATP synthase F1 sector gamma subunit / F-ATPase gamma subunit


Mass: 33439.836 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R201
#4: Protein ATP synthase epsilon chain / ATP synthase F1 sector epsilon subunit / F-ATPase epsilon subunit


Mass: 13277.741 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R1Z9
#5: Protein ATP synthase subunit b / / ATP synthase F(0) sector subunit b / ATPase subunit I / F-type ATPase subunit b / F-ATPase subunit b


Mass: 17636.701 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R204
#6: Protein ATP synthase subunit b-delta /


Mass: 47504.723 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R203
#7: Protein
ATP synthase subunit c /


Mass: 8597.982 Da / Num. of mol.: 9 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R205
#8: Protein ATP synthase subunit a /


Mass: 27568.482 Da / Num. of mol.: 1 / Source method: isolated from a natural source
Source: (natural) Mycolicibacterium smegmatis MC2 155 (bacteria)
References: UniProt: A0R206

-
Non-polymers , 4 types, 16 molecules

#9: Chemical
ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE / Adenosine triphosphate


Mass: 507.181 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Comment: ATP, energy-carrying molecule*YM
#10: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Mg
#11: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#12: Chemical
ChemComp-YGR / (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-2-(2,6-dimethoxypyridin-4-yl)-4-(dimethylamino)-1-(2,3,6-trimethoxypyridin-4-yl)butan-2-ol


Mass: 657.552 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C31H37BrN4O7 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: TBAJ-876-bound Mycobacterium smegmatis ATP synthase rotational state 1
Type: COMPLEX / Entity ID: #1-#8 / Source: NATURAL
Source (natural)Organism: Mycolicibacterium smegmatis MC2 155 (bacteria)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
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: 2100 nm / Nominal defocus min: 700 nm
Image recordingElectron dose: 44 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 96742 / Symmetry type: POINT

+
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