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

Molecular modeling of the H 4 -H 5 -loop of the a 2 isoform of Na + /K + -ATPase in the E 1 and E 2 conformations revealed that twisting of the nucleotide (N) domain toward the phosphorylation (P) domain is connected with the formation of a short n-helix between Asp 369 and Thr 3,5 . This conformational change close to the hinge region between the N-domain and the P-domain could be an important event leading to a bending of the N-domain by 64.7° and to a shortening of the distance between the ATP binding site and the phosphorylation site (Asp 369 ) by 1.22 nm from 3.22 nm to 2.00 nm. It is hypothesized that this shortening mechanism is involved in the Na + -dependent formation of the Asp 369 phospho-intermediate as part of the overall Na + /K + -ATPase activity.