7MET

A. baumannii MsbA in complex with TBT1 decoupler


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.97 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Distinct allosteric mechanisms of first-generation MsbA inhibitors.

Thelot, F.A.Zhang, W.Song, K.Xu, C.Huang, J.Liao, M.

(2021) Science 374: 580-585

  • DOI: https://doi.org/10.1126/science.abi9009
  • Primary Citation of Related Structures:  
    7MET, 7MEW, 7RIT

  • PubMed Abstract: 

    ATP-binding cassette (ABC) transporters couple adenosine 5′-triphosphate (ATP) hydrolysis to substrate transport across biological membranes. Although many are promising drug targets, their mechanisms of modulation by small-molecule inhibitors remain largely unknown. Two first-generation inhibitors of the MsbA transporter, tetrahydrobenzothiophene 1 (TBT1) and G247, induce opposite effects on ATP hydrolysis. Using single-particle cryo–electron microscopy and functional assays, we show that TBT1 and G247 bind adjacent yet separate pockets in the MsbA transmembrane domains. Two TBT1 molecules asymmetrically occupy the substrate-binding site, which leads to a collapsed inward-facing conformation with decreased distance between the nucleotide-binding domains (NBDs). By contrast, two G247 molecules symmetrically increase NBD distance in a wide inward-open state of MsbA. The divergent mechanisms of action of these MsbA inhibitors provide important insights into ABC transporter pharmacology.


  • Organizational Affiliation

    Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ATP-dependent lipid A-core flippase
A, B
607Acinetobacter baumanniiMutation(s): 0 
Gene Names: msbAAB71191_02689B9X95_12125DOL94_12040IX87_02345
EC: 7.5.2.6
Membrane Entity: Yes 
UniProt
Find proteins for A0A0B9X4I2 (Acinetobacter baumannii)
Explore A0A0B9X4I2 
Go to UniProtKB:  A0A0B9X4I2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0B9X4I2
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Z5G
Query on Z5G

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A]
2-(4-chlorobenzamido)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylic acid
C16 H14 Cl N O3 S
DUJFDTGMUKWELI-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.97 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2021-10-06
    Type: Initial release
  • Version 1.1: 2021-11-10
    Changes: Database references
  • Version 1.2: 2024-05-29
    Changes: Data collection