Figure 8. Proposed cycle for coupling ATPase with adenylate kinase activities in MsbA.

Next to the canonical ATP-binding sites (site 1), two additional ADP-binding sites (site 2) are proposed involving Walker B and Q-loop of one and D-loop of the other NBD (Fig. 4a). This model allows suggesting a catalytic cycle with an ATP bound (1), ADP bound (2), ATP+ADP bound (3), ADP saturated (4) and finally ATP+AMP bound (5) state (see also Fig. 4 and Supplementary Fig. 7). The steps needed for the primary ATPase reaction as part of the normal catalytic cycle are highlighted.