Comparative Modeling of the H-4-H-5-loop of the alpha(2)-isoform of Na+/K+-ATPase alpha-subunit in the E-1 conformation
Abstrakt
Restraint-based comparative modeling was used for calculation and visualization of the H-4-H-5-loop of Na+/K+-ATPase from mouse brain (Mus musculus, adult male brain, alpha(2)-isoform) between the amino acid residues Cys(336) and Arg(758) in the E-1 conformation The structure consists of two well separated parts. The N-domain is formed by a seven-stranded antiparallel beta-sheet with two additional beta-strands and five alpha-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 alpha(2)- and alpha(1)-isoforrns. The phosphorylation Asp 369 residue was found in the central part of the P-domain, located at the C-terminal end of the central beta-sheet.
The distance between the a-carbon of Phe(475) at the ATP-binding site and the alpha-carbon of ASP(369) at the phosphorylation site is 3.22 nm. A hydrogen bond between the oxygen atom of ASP(169) and the nitrogen atom of Lys(690) was clearly detected and assumed to play a key role in maintaining the proper structure of the physphorylaton site in E-1 conformation.