Fig. S1.

Na⁺,K⁺-ATPase reaction cycle. E₁ and E₂ represent the main conformational states of the enzyme that are Na⁺ selective and K⁺ selective, respectively. P indicates phosphorylation from ATP at the conserved aspartate of the P-type ATPase signature sequence. During the transport process, the Na⁺ and K⁺ ions become occluded [i.e., bound in the protein without access to the medium on either side of the membrane (shown in brackets)]. Free ions are labeled c and e for cytoplasmic and extracellular, respectively. The H⁺,K⁺-ATPase functions by a similar, but electroneutral, mechanism, with the 3 Na⁺ being replaced by 1 or 2 H⁺ and 1 or 2 K⁺ being countertransported.