Restraint-based comparative modeling was used for calculation and visualization of the H4-H5-loop of Na+/K+-ATPase from mouse brain (Mus musculus, adult male brain, α2-isoform) between the amino acid residues Cys336 and Arg758 in the E1 conformation The structure consists of two well separated parts. The N-domain is formed by a seven-stranded antiparallel β-sheet with two additional β-strands and five α-helices sandwiching it, the P-domain is composed of a typical Rossman fold. The ATP-binding site was found on the N-domain to be identical in both α2- and α1-isoforms. The phosphorylation Asp369 residue was found in the central part of the P-domain, located at the C-terminal end of the central β-sheet. The distance between the α-carbon of Phe475 at the ATP-binding site and the α-carbon of Asp369 at the phosphorylation site is 3.22 nm. A hydrogen bond between the oxygen atom of Asp369 and the nitrogen atom of Lys690 was clearly detected and assumed to play a key role in maintaining the proper structure of the physphorylaton site in E1 conformation., G. Tejral, L. Koláčná, A. Kotyk, E. Amler., and Obsahuje bibliografii
Molecular modeling of the H4-H5-loop of the α2 isoform of Na+/K+-ATPase in the E1 and E2 conformations revealed that twisting of the nucleotide (N) domain toward the phosphorylation (P) domain is connected with the formation of a short π-helix between Asp369 and Thr375. 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 (Asp369) 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 Asp369 phospho-intermediate as part of the overall Na+/K+-ATPase activity., G. Tejral ... [et al.]., and Obsahuje seznam literatury