Loveridge E Joel, Evans Rhiannon M, Allemann Rudolf K
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK.
Chemistry. 2008;14(34):10782-8. doi: 10.1002/chem.200801804.
Protein motions may be perturbed by altering the properties of the reaction medium. Here we show that dielectric constant, but not viscosity, affects the rate of the hydride-transfer reaction catalysed by dihydrofolate reductase from Thermotoga maritima (TmDHFR), in which quantum-mechanical tunnelling has previously been shown to be driven by protein motions. Neither dielectric constant nor viscosity directly alters the kinetic isotope effect of the reaction or the mechanism of coupling of protein motions to tunnelling. Glycerol and sucrose cause a significant increase in the rate of hydride transfer, but lead to a reduction in the magnitude of the kinetic isotope effect as well as an extension of the temperature range over which "passive" protein dynamics (rather than "active" gating motions) dominate the reaction. Our results are in agreement with the proposal that non-equilibrium dynamical processes (promoting motions) drive the hydride-transfer reaction in TmDHFR.
通过改变反应介质的性质，蛋白质运动可能会受到干扰。我们在此表明，介电常数而非粘度会影响嗜热栖热菌二氢叶酸还原酶（TmDHFR）催化的氢化物转移反应速率，此前已证明该反应中的量子力学隧穿是由蛋白质运动驱动的。介电常数和粘度均不会直接改变反应的动力学同位素效应或蛋白质运动与隧穿的耦合机制。甘油和蔗糖会使氢化物转移速率显著增加，但会导致动力学同位素效应的幅度降低，以及“被动”蛋白质动力学（而非“主动”门控运动）主导反应的温度范围扩大。我们的结果与非平衡动力学过程（促进运动）驱动TmDHFR中氢化物转移反应的提议一致。
