Kumauchi Masato, Hamada Norio, Sasaki Jun, Tokunaga Fumio
Department of Earth and Space Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
J Biochem. 2002 Aug;132(2):205-10. doi: 10.1093/oxfordjournals.jbchem.a003211.
PYP (photoactive yellow protein) is a photoreceptor protein, which is activated upon photo-isomerization of the p-coumaric acid chromophore and is inactivated as the chromophore is thermally back-isomerized within a second (in PYP(M)-to-PYP(dark) conversion). Here we have examined the mechanism of the rapid thermal isomerization by analyzing mutant PYPs of Met100, which was previously shown to play a major role in facilitating the reaction [Devanathan, S. et al. (1998) Biochemistry 37, 11563-11568]. The mutation to Lys, Leu, Ala, or Glu decelerated the dark state recovery by one to three orders of magnitude. By evaluating temperature-dependence of the kinetics, it was found that the retardation resulted unequivocally from elevations of activation enthalpy (DeltaH( double dagger )) but not the other parameters such as activation entropy or heat capacity changes. Another effect exerted by the mutations was an up-shift of the apparent pK(a) of the chromophore [the pK(a) of a titratable group (X) that controls the pK(a) of the chromophore] in the PYP(M)-decay process. The pK(a) up-shift and the DeltaH( double dagger ) elevation show an approximately linear correlation. We, therefore, postulate that the role of Met100 is to reduce the energy barrier of the PYP(M)-decay process by an indirect interaction through X and that the process is thereby facilitated.
光敏黄色蛋白(PYP)是一种光受体蛋白,在对香豆酸发色团发生光异构化时被激活,而当发色团在一秒内发生热逆向异构化时(从PYP(M)转变为PYP(暗态))则失活。在此,我们通过分析Met100的突变型PYP来研究快速热异构化的机制,此前已表明Met100在促进该反应中起主要作用[Devanathan, S.等人(1998年)《生物化学》37卷,11563 - 11568页]。将其突变为赖氨酸、亮氨酸、丙氨酸或谷氨酸会使暗态恢复速度减慢一到三个数量级。通过评估动力学的温度依赖性,发现这种减慢明确是由活化焓(ΔH‡)升高导致的,而非其他参数,如活化熵或热容变化。这些突变产生的另一个影响是在PYP(M)衰减过程中发色团表观pKa的上移[控制发色团pKa的可滴定基团(X)的pKa]。pKa上移与ΔH‡升高呈现近似线性关系。因此,我们推测Met100的作用是通过与X的间接相互作用降低PYP(M)衰减过程的能量屏障,从而促进该过程。