The π-helix formation between Asp369 and Thr375 as a key factor in E1-E2 conformational change of Na+/K+-ATPase

Molecular modeling of the H4-H5-loop of the α2 isoform of Na+/K+-ATPase in the E1 and E2 conformations revealed that twisting ofthe nucleotide (N) domain toward the phosphorylation (P)domain is connected with the formation of a short π-helixbetween Asp369 and Thr375. This conformational change close tothe hinge region between the N-domain and the P-domain couldbe an important event leading to a bending of the N-domain by64.7° and to a shortening of the distance between the ATPbinding site and the phosphorylation site (Asp369) by 1.22 nmfrom 3.22 nm to 2.00 nm. It is hypothesized that this shorteningmechanism is involved in the Na+-dependent formation of theAsp369 phospho-intermediate as part of the overall Na+/K+-ATPase activity.