Fig. 5. Proposed model for lipid transport by MtEfpA and small-molecule inhibition.

a Lipid transport model for MtEfpA and distinct target sites of different inhibitors. NTD, N-terminal domain. HD, hinge domain. CTD, C-terminal domain. The substrate lipid flips to adjacent binding site or releases to the outer-leaf of membrane during each conformational transition. BRD-8000.3 targets lipid-binding site A and BRD-9327 was supposed to target lipid-binding site B to inhibit MtEfpA function. b Lipids undergo a stepwise flipping, resembling a staircase, from the inner leaflet to the outer leaflet of the membrane.