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Open data
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Basic information
Entry | Database: PDB / ID: 7rit | ||||||
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Title | Drug-free A. baumannii MsbA | ||||||
![]() | ATP-dependent lipid A-core flippase | ||||||
![]() | MEMBRANE PROTEIN | ||||||
Function / homology | ![]() ATPase-coupled lipid transmembrane transporter activity / ABC-type transporter activity / ATP hydrolysis activity / ATP binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.2 Å | ||||||
![]() | Thelot, F. / Liao, M. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Distinct allosteric mechanisms of first-generation MsbA inhibitors. Authors: François A Thélot / Wenyi Zhang / KangKang Song / Chen Xu / Jing Huang / Maofu Liao / ![]() ![]() 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 ...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. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 165.5 KB | Display | ![]() |
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PDB format | ![]() | 112.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 699.7 KB | Display | ![]() |
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Full document | ![]() | 701.7 KB | Display | |
Data in XML | ![]() | 27.4 KB | Display | |
Data in CIF | ![]() | 43.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 23804MC ![]() 7metC ![]() 7mewC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: motion-corrected micrographs for drug-free A. baumannii MsbA [micrographs - single frame]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 67758.688 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: msbA, AWN74_06935, B9X95_12125, BS098_14620, D3X55_14335, DOL94_12040, IX87_02345, SI89_17920 Production host: ![]() ![]() References: UniProt: A0A0B9X4I2, ABC-type lipid A-core oligosaccharide transporter |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Drug-free A. baumannii MsbA / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.13 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: OTHER |
Image recording | Electron dose: 52 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C2 (2 fold cyclic) |
3D reconstruction | Resolution: 5.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 25417 / Symmetry type: POINT |