Involved in lipopolysaccharide (LPS) biosynthesis. Translocates lipid A-core from the inner to the outer leaflet of the inner membrane (PubMed:8809774, PubMed:9575204, PubMed:12119303, PubMed:15304478, PubMed:28869968). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (PubMed:12119303). Shows ATPase activity (PubMed:12119303, PubMed:18024585, PubMed:18344567, PubMed:19132955, PubMed:20412049, PubMed:21462989). May transport glycerophospholipids (PubMed:9575204). In proteoliposomes, mediates the ATP-dependent flipping of a variety of phospholipid and glycolipid derivatives (PubMed:20412049). May also function as a multidrug transporter (PubMed:19132955). ATP + H2O + lipid A-core oligosaccharideSide 1 = ADP + phosphate + lipid A-core oligosaccharideSide 2. ATPase activity is stimulated by lipid A, hexaacylated lipid A or Kdo(2)-lipid A (PubMed:12119303, PubMed:18344567). Inhibited by the phosphate analog vanadate (PubMed:12119303, PubMed:18344567, PubMed:28869968). ATPase activity is also modulated by the lipid-based drugs D-20133 and D-21266, along with LY335979 and leupeptin (PubMed:18344567). Homodimer. In MsbA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. Substrate binding induces conformational changes, NBD dimerization, and stabilizes an inward-facing closed pre-translocation state that binds ATP (PubMed:18344567, PubMed:23766512, PubMed:28869968). ATP binding fuels a relative motion of the NBD domains. The movement of the NBDs is coupled to reorientation of the chamber, which binds the lipid substrate, from cytoplasmic-facing to periplasmic-facing through large amplitude motion on either side of the transporter (PubMed:17927448, PubMed:20715055, PubMed:18024585, PubMed:28869968). ATP hydrolysis is then required to resolve the outward-facing conformation back to an inward-facing conformation (PubMed:23766512, PubMed:28869968). The ATP-dependent switch requires robust tetrahelix bundle interactions (PubMed:23306205). Contains two substrate-binding sites that communicate with both the nucleotide-binding domain and with each other. One is a high affinity binding site for the physiological substrate, lipid A, and the other site interacts with drugs with comparable affinity. Absence of MsbA alone causes accumulation of hexa-acylated lipid A species and glycerophospholipids in the inner membrane. In addition to ATP hydrolysis, may utilize another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient (PubMed:27499013). In vitro, MsbA-mediated ethidium efflux is dependent on both the electrochemical proton gradient and ATP hydrolysis (PubMed:27499013). Identified as a drug target. Inhibited by a series of quinoline compounds that kill E.coli through inhibition of ATPase and transport activity of MsbA. Belongs to the ABC transporter superfamily. Lipid exporter (TC 3.A.1.106) family.