Binding affinities and protein ligand complex geometries of nucleotides at the F1 part of the mitochondrial ATP synthase obtained by ligand docking calculations

FEBS Letters

Hucke, Oliver¹  Steinbrecher, Thomas¹  Steigmiller, Stefan¹  Labahn, Andreas¹  Börsch, Michael¹ 

[1] Institut für Physikalische Chemie der Albert-Ludwigs-Universität Freiburg, Albertstraße 23a, D-79104 Freiburg, Germany

关键词: ATP synthase;    Ligand docking;    Fluorescent ATP derivatives;    MF1;    F1 part of the mitochondrial F0F1 ATP synthase;    EF1;    F1 part of the F0F1 ATP synthase from E. coli;    BODIPY-FL-ATP;    adenosine 5′-triphosphate;    BODIPY® FL 2′-(or-3′)-O-(N-(2-aminoethyl) urethane);    BODIPY-TR-ATP;    adenosine 5′-triphosphate;    BODIPY® TR 2′-(or-3′)-O-(N-(2-aminoethyl) urethane);   

DOI  :  10.1016/S0014-5793(02)03433-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

F₀F₁ 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 F₁ 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.

【 授权许可】

Unknown