Browsing by Subject "BOUND UBIQUINONE"

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  • Haapanen, Outi; Sharma, Vivek (2021)
    Respiratory complex I is a key enzyme in the electron transport chains of mitochondria and bacteria. It transfers two electrons to quinone and couples this redox reaction to proton pumping to electrically charge the membrane it is embedded in. The charge and pH gradient across the membrane drives the synthesis of ATP. The redox reaction and proton pumping in complex I are separated in space and time, which raises the question of how the two reactions are coupled so efficiently. Here, we focus on the unique similar to 35 angstrom long tunnel of complex I, which houses the binding site of quinone reduction. We discuss the redox and protonation reactions that occur in this tunnel and how they influence the dynamics of protein and substrate. On the basis of recent structural data and results from molecular simulations, we review how quinone reduction and dynamics may be coupled to proton pumping in complex I.
  • Haapanen, Outi; Djurabekova, Amina; Sharma, Vivek (2019)
    Respiratory complex I performs the reduction of quinone (Q) to quinol (QH(2)) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (similar to 30 angstrom) and unique substrate binding channel. However, due to missing structural information on Q binding modes, it remains unclear how Q reduction drives long range (similar to 20 nm) redox-coupled proton pumping in complex I. Here we applied multiscale computational approaches to study the dynamics and redox chemistry of Q and QH(2). Based on tens of microseconds of atomistic molecular dynamics (MD) simulations of bacterial and mitochondrial complex I, we find that the dynamics of Q is remarkably rapid and it diffuses from the N2 binding site to another stable site near the entrance of the Q channel in microseconds. Analysis of simulation trajectories also reveal the presence of yet another Q binding site 25-30 angstrom from the N2 center, which is in remarkable agreement with the electron density observed in recent cryo electron microscopy structure of complex I from Yarrowia lipolytica. Quantum chemical computations on the two Q binding sites closer to the entrance of the Q tunnel reveal redox-coupled protonation reactions that may be important in driving the proton pump of complex I.