Binding affinities and protein ligand complex geometries of nucleotides at the F(1) part of the mitochondrial ATP synthase obtained by ligand docking calculations.
F(0)F(1) ATP synthases utilize a transmembrane electrochemical potential difference to synthesize ATP from ADP and phosphate. In this work, the binding modes of ADP, ATP and ATP analogues to the catalytic sites of the F(1) part of the mitochondrial ATP synthase were investigated with ligand docking calculations. Binding geometries of ATP and ADP at the three catalytic sites agree with X-ray crystal data; their binding free energies suggest an assignment to the 'tight', 'open' and 'loose' states. The rates of multi-site hydrolysis for two fluorescent ATP derivatives were measured using a fluorescence assay. Reduced hydrolysis rates compared to ATP can be explained by the ligand docking calculations.
Steinbrecher
Thomas
T
Institut für Physikalische Chemie der Albert-Ludwigs-Universität Freiburg, Albertstrasse 23a, Germany.
Hucke
Oliver
O
Steigmiller
Stefan
S
Börsch
Michael
M
Labahn
Andreas
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000465:Algorithms; D018360:Crystallography, X-Ray; D006868:Hydrolysis; D008024:Ligands; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D011485:Protein Binding; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases