Three-dimensional structure of the large cytoplasmic H4–H5 loop of Na+/K+-ATPase deduced by restraint-based comparative modeling shows only one ATP binding site.

Autor: Ettrich, Rüdiger, Melichercik, Milan, Teisinger, Jan, Ettrichova, Olga, Krumscheid, Rita, Hofbauerova, Katerina, Kvasnicka, Peter, Schoner, Wilhelm, Amler, Evzen
Zdroj: Journal of Molecular Modeling; Jun2001, Vol. 7 Issue 6, p184-192, 9p
Abstrakt: Homology modeling of the complete structure of the large cytoplasmic loop between the fourth and fifth transmembrane segments (H4–H5 loop) of the α subunit of Na+/K+-ATPase is reported. The deduced amino acid sequence shows high sequence identity and homology to the Ca2+-ATPase (32.8% identity and 53.3% similarity in our alignment), whose tertiary structure has been solved recently at 2.6-Å resolution by X-ray crystallography. This high homology allowed the construction of a model structure using the MODELLER program. Refinement was achieved through interactive visual and algorithmic analysis and minimization with the TRIPOS force field included in the SYBYL/MAXIMIN2 module. The docking of ATP as a substrate into the active site of the model was explored with the AUTODOCK program followed by molecular mechanics optimization of the most interesting complexes. Thus, the docking of ATP into the resulting model of the H4–H5 loop gave evidence for the existence of one ATP binding site only. We were able to specify Cys549, Phe548, Glu505, Lys501, Gln482, Lys480, Ser477, Phe475 and Glu446 as parts of the ATP binding site with Lys501 located in the depth of the positively charged binding pocket. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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