Characterization of 2- and 3-Methoxy in Ubiquinone Binding and Redox Tuning within the Photosynthetic Reaction Center of Rhodobacter Sphaeroides

Abstract

Ubiquinone is a universal, membrane-associated redox mediator. The redox properties of ubiquinone in vivo are closely controlled both by its electrostatic environment within the binding sites of proteins and by steric interactions determining its conformation. Recent experimental work suggests that differences in the angle of the two methoxy side chains with respect to the quinone ring plane dictate the redox potential difference between the two quinone binding sites, however the specific quinone-protein interactions that alter the redox potential could not be identified.In order to ascertain which specific interactions between the quinones and their environment tune the redox potential, molecular dynamics simulations of ubiquinone bound to the QA and QB sites of the photosynthetic reaction center (RC) of Rhodobacter Sphaeroides were compared with complementary studies done on ubiquinone analogs lacking either the 2- or 3-methoxy group. Since prior ubiquinone parameters were biased towards non-native methoxy angles, systematically parameterized ubiquinone and its analogues to accurately describe the structure and dynamics of the methoxy groups.The removal any methoxy group showed little impact on the QA binding. However, both the binding conformation and the methoxy dihedral angle distribution in the QB site were significantly altered upon removal of the 2-methoxy group. We observe that the 2-methoxy group in the QB site is oriented approximately normal to the ring plane. This orientation is favored by a weak hydrogen bond between the 2-methoxy oxygen and the amine of GLY225. A more out of plane methoxy (as imposed by the protein environment) would correspond to a higher electron affinity of QB over QA. We propose this hydrogen bond as the mechanism whereby the redox potential is tuned to promote inter-quinone electron transfer in the RC.