Practice question

Active maintenance of sodium and potassium gradients consumes significant portion of cellular ATP budget, about one third in neurons, mediated by Na+/K+ ATPase discovered by Skou. P-type pump cycle begins in E1 conformation with ion binding site open to cytoplasm high affinity for sodium, coordinating three sodium ions using side chain carboxyls of Glu327, Glu776, Asp804 and backbone carbonyls in M4-M6. ATP binds N domain, phosphorylates Asp369 in P domain forming E1P occluded state. Transition to E2P lowers sodium affinity releasing ions extracellularly where sodium about 145 millimolar. Cavity now reorganized high affinity for potassium accommodating two potassium ions via similar carbonyl coordination requiring smaller dehydration energy. Potassium binding triggers dephosphorylation by A domain TGES motif generating E2 with occluded K+ then conversion to E1 opening intracellular releasing K+ where affinity weak. Net exchange three Na+ outward, two K+ inward per ATP, electrogenic exporting one positive charge, contributing to negative interior and enabling secondary active processes like SGLT and NCX. Inhibitor ouabain binds E2P extracellular vestibule.