tailieunhanh - Báo cáo Y học: Exploring the primary electron acceptor (QA)-site of the bacterial reaction center from Rhodobacter sphaeroides Binding mode of vitamin K derivatives

The functional replacement of the primary ubiquinone (QA) in the photosynthetic reaction center (RC) from Rhodo-bacter sphaeroideswith synthetic vitamin K derivatives has provided a powerful tool to investigate the electron transfer mechanism. To investigate the binding mode of these qui-nones to theQAbinding sitewe have determined the binding free energy and charge recombination rate from QA ± to D + (kAD) of 29 different 1,4-naphthoquinone derivatives with systematically altered structures. | Eur. J. Biochem. 269 1096-1108 2002 FEBS 2002 Exploring the primary electron acceptor QA -site of the bacterial reaction center from Rhodobacter sphaeroides Binding mode of vitamin K derivatives Oliver Hucke Ralf Schmid and Andreas Labahn Institut fur Physikalische Chemie Albert-Ludwigs-Universitat Freiburg Germany The functional replacement of the primary ubiquinone QA in the photosynthetic reaction center RC from Rhodo-bacter sphaeroides with synthetic vitamin K derivatives has provided a powerful tool to investigate the electron transfer mechanism. To investigate the binding mode of these quinones to the QA binding site we have determined the binding free energy and charge recombination rate from QA to D kAD of 29 different 1 4-naphthoquinone derivatives with systematically altered structures. The most striking result was that none of the eight tested compounds carrying methyl groups in both positions 5 and 8 of the aromatic ring exhibited functional binding. To understand the binding properties of these quinones on a molecular level the structures of the reaction center-naphthoquinone complexes were predicted with ligand docking calculations. All proteinligand structures show hydrogen bonds between the carbonyl oxygens of the quinone and AlaM260 and HisM219 as found for the native ubiquinone-10 in the X-ray structure. The center-to-center distance between the naphthoquinones at QA and the native ubiquinone-10 at QB the secondary electron acceptor is essentially the same compared to the native structure. A detailed analysis of the docking calculations reveals that 5 8-disubstitution prohibits binding due to steric clashes of the 5-methyl group with the backbone atoms of AlaM260 and AlaM249. The experimentally determined binding free energies were reproduced with an rmsd of w 4 kJ-mol-1 in most cases providing a valuable tool for the design of new artificial electron acceptors and inhibitors. Keywords ligand docking structure activity relationship bacterial .