46 research outputs found
Mechanism of long-range proton translocation along biological membranes
AbstractRecent experiments suggest that protons can travel along biological membranes up to tens of micrometers, but the mechanism of transport is unknown. To explain such a long-range proton translocation we describe a model that takes into account the coupled bulk diffusion that accompanies the migration of protons on the surface. We show that protons diffusing at or near the surface before equilibrating with the bulk desorb and re-adsorb at the surface thousands of times, giving rise to a power-law desorption kinetics. As a result, the decay of the surface protons occurs very slowly, allowing for establishing local gradient and local exchange, as was envisioned in the early local models of biological energy transduction
Theoretical and computational analysis of the membrane potential generated by cytochrome c oxidase upon single electron injection into the enzyme
AbstractWe have developed theory and the computational scheme for the analysis of the kinetics of the membrane potential generated by cytochrome c oxidase upon single electron injection into the enzyme. The theory allows one to connect the charge motions inside the enzyme to the membrane potential observed in the experiments by using data from the âdielectric topographyâ map of the enzyme that we have created. The developed theory is applied for the analysis of the potentiometric data recently reported by the Wikström group [I. Belevich, D.A. Bloch, N. Belevich, M. Wikström and M.I. Verkhovsky, Exploring the proton pump mechanism of cytochrome c oxidase in real time, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 2685â2690] on the O to E transition in Paracoccus denitrificans oxidase. Our analysis suggests, that the electron transfer to the binuclear center is coupled to a proton transfer (proton loading) to a group just âaboveâ the binuclear center of the enzyme, from which the pumped proton is subsequently expelled by the chemical proton arriving to the binuclear center. The identity of the pump site could not be determined with certainty, but could be localized to the group of residues His326 (His291 in bovine), propionates of heme a3, Arg 473/474, and Trp164. The analysis also suggests that the dielectric distance from the P-side to Fe a is 0.4 or larger. The difficulties and pitfalls of quantitative interpretation of potentiometric data are discussed
Computer simulation of water in cytochrome c oxidase
AbstractStatistical mechanics and molecular dynamics simulations have been carried out to study the distribution and dynamics of internal water molecules in bovine heart cytochrome c oxidase (CcO). CcO is found to be capable of holding plenty of water, which in subunit I alone amounts to about 165 molecules. The dynamic characterization of these water molecules is carried out. The nascent water molecules produced in the redox reaction at the heme a3âCuB binuclear site form an intriguing chain structure. The chain begins at the position of Glu242 at the end of the D channel, and has a fork structure, one branch of which leads to the binuclear center, and the other to the propionate d of heme a3. The branch that leads to the binuclear center has dynamic access both to the site where the formation of water occurs, and to delta-nitrogen of His291. From the binuclear center, the chain continues to run into the K channel. The stability of this hydrogen bond network is examined dynamically. The catalytic site is located at the hydrophobic region, and the nascent water molecules are produced at the top of the energy hill. The energy gradient is utilized as the mechanism of water removal from the protein. The water exit channels are explored using high-temperature dynamics simulations. Two putative channels for water exit from the catalytic site have been identified. One is leading directly toward Mg2+ site. However, this channel is only open when His291 is dissociated from CuB. If His291 is bound to CuB, the only channel for water exit is the one that originates at E242 and leads toward the middle of the membrane. This is the same channel that is presumably used for oxygen supply
Polarizable molecular interactions in condensed phase and their equivalent nonpolarizable models
Earlier, using phenomenological approach, we showed that in some cases
polarizable models of condensed phase systems can be reduced to nonpolarizable
equivalent models with scaled charges. Examples of such systems include ionic
liquids, TIPnP-type models of water, protein force fields, and others, where
interactions and dynamics of inherently polarizable species can be accurately
described by nonpolarizable models. To describe electrostatic interactions, the
effective charges of simple ionic liquids are obtained by scaling the actual
charges of ions by a factor of 1/sqrt(eps_el), which is due to electronic
polarization screening effect; the scaling factor of neutral species is more
complicated. Here, using several theoretical models, we examine how exactly the
scaling factors appear in theory, and how, and under what conditions,
polarizable Hamiltonians are reduced to nonpolarizable ones. These models allow
one to trace the origin of the scaling factors, determine their values, and
obtain important insights on the nature of polarizable interactions in
condensed matter systems.Comment: 43 pages, 3 figure
The Kinetics of Autoxidation in Wine
The kinetics of autoxidation in wine begins with Fenton (1876) who observed that tartaric acid could be oxidized in the presence of iron without peroxide if left in air. Rodopulo (1951) demonstrated that iron tartrate complexes added to wine promoted more extensive oxygen consumption than the molar equivalent of inorganic ferrous or ferric salts. The role of iron complexes in the activation of oxygen, the formation of reactive oxygen species and the initiation of autoxidation are crucial for understanding wine oxidation kinetics. Mechanisms based on hydroxyl radicals versus the ferryl species are likely to have different oxidation products of wine components based on pH effects. The ferryl ion, hydroxyl radical, and tartaric acid radical are proposed as key intermediates in the proposed general mechanism for hydrogen peroxide formation and the autoxidation of wine components. A quantitative kinetic description is presented for the autoxidation of tartaric acid and extended to other acid components as potential ligands. This chapter explores the theoretical considerations of iron complexes formation, oxygen activation, an autoxidative mechanism, and experimental measurements of tartaric acid oxidation as the basis of autoxidation in wine
Recommended from our members
Redox-Driven Proton Pumps of the Respiratory Chain
In aerobic cells, the proton gradient that drives ATP synthesis is created by three different proton pumps-membrane enzymes of the respiratory electron transport chain known as complex I, III, and IV. Despite the striking dissimilarity of structures and apparent differences in molecular mechanisms of proton pumping, all three enzymes have much in common and employ the same universal physical principles of converting redox energy to proton pumping. In this study, we describe a simple mathematical model that illustrates the general principles of redox-driven proton pumps and discuss their implementation in complex I, III, and IV of the respiratory chain