7MET
A. baumannii MsbA in complex with TBT1 decoupler
Summary for 7MET
| Entry DOI | 10.2210/pdb7met/pdb |
| EMDB information | 23803 |
| Descriptor | ATP-dependent lipid A-core flippase, 2-(4-chlorobenzamido)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylic acid (2 entities in total) |
| Functional Keywords | membrane protein |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 2 |
| Total formula weight | 136188.99 |
| Authors | Thelot, F.,Liao, M. (deposition date: 2021-04-07, release date: 2021-10-06, Last modification date: 2024-05-29) |
| Primary citation | Thelot, F.A.,Zhang, W.,Song, K.,Xu, C.,Huang, J.,Liao, M. Distinct allosteric mechanisms of first-generation MsbA inhibitors. Science, 374:580-585, 2021 Cited by 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. PubMed: 34554829DOI: 10.1126/science.abi9009 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.97 Å) |
Structure validation
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