Molecular Mechanisms of Energy Transduction in Cells: Engineering Applications and Biological Implications

Lessons Learned from UvrD Helicase: Mechanism for Directional Movement

“…All motor proteins require electrochemical energy to overcome random thermal diffusion and produce directional motion (12). The most well known and best studied of motorized processes include actin-myosin based muscle contraction (29, 41–43, 57, 73), flagella-propelled bacteria or sperm cell movement (44, 97), microtubule-kinesin facilitated cargo transport (30, 38), membrane transporters moving molecules against concentration gradients (37, 66, 78, 83), and various helicases, which can separate double helices, alter DNA and RNA structures, and translocate, package or remodel genomic DNA (34, 80, 81, 91, 93). All motor proteins depend on chemical or electrical energy to perform mechanical work.…”

Interpretation of the mechanism of action of antituberculosis drug bedaquiline based on a novel two‐ion theory of energy coupling in ATP synthesis

“…It is proposed here that a novel, chemically attractive explanation and resolution of the above crucial issues lies in the fact that under the experimental conditions of Hards et al and Lamprecht et al that employ an 80‐fold or a 30‐fold to 300‐fold higher concentration of bedaquiline respectively, relative to its minimum inhibitory concentration, an H + /K + antiport ionophore mechanism of bedaquiline and an uncoupling mode of action of the drug discussed above is operative, in accord with the central tenets of Nath's torsional mechanism in ATP synthase and two‐ion theory of energy coupling/uncoupling . The collapse of the H + and K + electrochemical gradients induced by the H + /K + exchange function of bedaquiline and the resulting uncoupling of ATP synthesis is responsible for the observed stimulation of oxygen consumption in M. smegmatis and M. tuberculosis …”

“…For further details, please refer to the text. The case of the combined operation of (a) and (B) has already been discussed and quantitatively analyzed during the conception and detailed formulation of Nath's torsional mechanism of energy transduction and ATP synthesis (e.g., in Reference , see especially table 2 of section 3.4 and eqs. 1–9)…”

“…It is proposed here that a novel, chemically attractive explanation and resolution of the above crucial issues lies in the fact that under the experimental conditions of Hards et al 21 and Lamprecht et al 36 that employ an 80-fold or a 30-fold to 300-fold higher concentration of bedaquiline respectively, relative to its minimum inhibitory concentration, an H + /K + antiport ionophore mechanism of bedaquiline and an uncoupling mode of action of the drug discussed above is operative, in accord with the central tenets of Nath's torsional mechanism in ATP synthase and two-ion theory of energy coupling/uncoupling. 12,13,28,37 The collapse of the H + and K + electrochemical gradi- Regardless, the ability of bedaquiline to dissipate both the ΔpH and the ΔpK due to its activity as a genuine H + /K + antiporter, but not the Δψ arising from succinate translocation (Figure 2A inside, or what is electrically equivalent, from a translocation of K + from inside to outside. It should be noted that events within the energy-transducing membrane can be rapidly communicated to the bulk aqueous phases.…”

“…The case of the combined operation of (a) and (B) has already been discussed and quantitatively analyzed during the conception and detailed formulation of Nath's torsional mechanism of energy transduction and ATP synthesis (e.g., in Reference 37, see especially table 2 of section 3.4 and eqs. 1-9) 37 is, H + and succinate/K + , respectively. Failure to consider the critical role of the "second ion" that is also involved in biological energy transduction along with protons leads to inconsistencies and incorrect interpretations and has been shown to be the fundamental reason underlying past and present difficulties.…”