Three-dimensional structure of the large cytoplasmic H-4-H-5 loop of Na(+)/K(+)-ATPase deduced by restraint-based comparative modeling shows only one ATP binding site

Ettrich, Rüdiger; Melicherčík, M.; Teisinger, Jan; Ettrichová, Olga; Krumscheid, R.; Hofbauerová, Kateřina; Kvasnička, P.; Schoner, W.; Amler, Evžen

Number of the records: 1

Three-dimensional structure of the large cytoplasmic H-4-H-5 loop of Na(+)/K(+)-ATPase deduced by restraint-based comparative modeling shows only one ATP binding site

1.

SYSNO ASEP	0142192
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Ostatní články
Title	Three-dimensional structure of the large cytoplasmic H-4-H-5 loop of Na(+)/K(+)-ATPase deduced by restraint-based comparative modeling shows only one ATP binding site
Author(s)	Ettrich, Rüdiger (FGU-C) Melicherčík, M. (SK) Teisinger, Jan (FGU-C)_RID Ettrichová, Olga (FGU-C) Krumscheid, R. (DE) Hofbauerová, Kateřina (FGU-C) Kvasnička, P. (SK) Schoner, W. (DE) Amler, Evžen (FGU-C)
Source Title	Journal of Molecular Modeling. - : Springer - ISSN 1610-2940 Roč. 7, č. 6 (2001), s. 184-192
Number of pages	9 s.
Language	eng - English
Country	US - United States
Keywords	Sodium potassium adenosine triphosphate ; tertiary structure ; adenosine triphosphate binding site
Subject RIV	BO - Biophysics
R&D Projects	VS961410 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	GA204/98/0468 GA ČR - Czech Science Foundation (CSF)
	IAA7011801 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
	GA204/98/0416 GA ČR - Czech Science Foundation (CSF)
CEZ	AV0Z5011922 - FGU-C
Annotation	Homology modeling of the complete structure of the large cytoplasmic loop between the fourth and fifth transmembrane segments (H4-H5 loop) of the alpha 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-A 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.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2002

Number of the records: 1