What happens if a mutation occurs in the phosphorylation site of Na+/K+ ATPase?
P-type ATPases operate through an ordered Post-Albers cycle involving transient phosphorylation of a conserved aspartate within the DKTGTLT motif of the cytosolic P-domain. ATP phosphorylates this aspartate in E1 state with high Na+ affinity open inward, generating E1-P with occluded Na+, then conversion to E2-P with outward openness and high K+ affinity releases Na+ and binds K+. Dephosphorylation returns enzyme to E2 and E1 states. Phosphorylation triggers long-range movement of nucleotide-binding N domain and actuator A domain, coupling chemical energy to alternating access. A missense or d
Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 11, P-type ATPases E1-E2 mechanism.
