8UFE
Multidrug efflux pump EfpA from mycobacterium smegmatis
Summary for 8UFE
| Entry DOI | 10.2210/pdb8ufe/pdb |
| Related | 8UFD 8WM5 |
| EMDB information | 42205 |
| Descriptor | Integral membrane efflux protein EfpA, PHOSPHATIDYLETHANOLAMINE (2 entities in total) |
| Functional Keywords | multidrug efflux pump, efpa, mycobacterium smegmatis, transport protein |
| Biological source | Mycolicibacterium smegmatis |
| Total number of polymer chains | 1 |
| Total formula weight | 49133.95 |
| Authors | |
| Primary citation | Wang, S.,Wang, K.,Song, K.,Lai, Z.W.,Li, P.,Li, D.,Sun, Y.,Mei, Y.,Xu, C.,Liao, M. Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition. Nat Commun, 15:7710-7710, 2024 Cited by PubMed Abstract: As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs. PubMed: 39231991DOI: 10.1038/s41467-024-51948-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.68 Å) |
Structure validation
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