8ufe | pdb_00008ufe

Multidrug efflux pump EfpA from mycobacterium smegmatis

spinqualitylabelsall models 8ufe, resolution 3.68Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ufe is a 1 chain structure with sequence from Mycolicibacterium smegmatis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.68Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A653FLF0_MYCSM Publication Abstract from PubMed 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. Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.,Wang S, Wang K, Song K, Lai ZW, Li P, Li D, Sun Y, Mei Y, Xu C, Liao M Nat Commun. 2024 Sep 4;15(1):7710. doi: 10.1038/s41467-024-51948-9. PMID:39231991 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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