Relevant functional and structural properties of the Na ⁺ /K ⁺ pump. (A) Post-Albers kinetic scheme describing partial reactions in the Na⁺/K⁺ pump cycle. (B) Overall view of the Na⁺/K⁺ pump structure in E1(3Na⁺) form, PDB accession no. 3WGV. The boxed part shows the ion-binding region (with three Na⁺ ions as blue spheres; see further below). In the cytoplasmic region, the nucleotide, phosphate analog (both in blue stick representation) and phosphorylated aspartate (stick representation in color by elements) are shown. (C) Zoomed-in view of the ion-binding region of the E1(3Na⁺) structure showing amino-acid side chains participating in ion coordination, as well as Y780 and surrounding residues (stick representation in color by elements). Broken lines indicate potential hydrogen bonds from Y780 (2.77 indicates the length in A of the bond between Y780 hydroxyl and T816 backbone oxygen). Numbers on the Na⁺-ions (blue spheres) are the ion-binding site number. (D) Zoomed-in view of the ion binding region of E2P_i(2K⁺) structure (PDB accession no. 2ZXE) with the same residues shown. K⁺ ions and a water molecule are shown as purple spheres and a red sphere, respectively. Broken lines indicate potential hydrogen bonds from Y780 (2.73 indicates the length in A of the bond between Y780 hydroxyl and D817 side-chain oxygen). Note that Y780 exchanges its hydrogen-bonding partner from T816 to D817 in connection with the E1–E2 conformational change (in E2 the length between Y780 hydroxyl and T816 backbone oxygen has increased to 4.95 A). (E) Amino-acid sequence alignment of the catalytic subunit of P-type-ATPases showing high conservation of the tyrosine residue studied in this article. P2-ATPaseses shown are Na⁺,K⁺-ATPase α1 subunit (NKA), the gastric H⁺,K⁺-ATPase α subunit (HKA), the plasma membrane Ca²⁺-ATPase catalytic subunit (PMCA), and the sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase catalytic subunit (SERCA). Other P-type ATPases indicated are the Cu-ATPase ATP7B (P1-ATPase), the H⁺-ATPase from Arabidopsis thaliana (P3-ATPase), and the human flippase ATP8A1 (P4-ATPase).