Acquisition of pro-oxidant activity of fALS-linked SOD1 mutants as revealed using circular dichroism and UV-resonance Raman spectroscopy

作者：Fujimaki Nobuhiro; Nishiya Ken; Miura Takashi; Nakabayashi Takakazu^*

来源：Chemical Physics, 2016, 479: 5-10.

DOI：10.1016/j.chemphys.2016.08.029

The acquisition of pro-oxidant activity of the mutated form of human Cu, Zn-superoxide dismutase (SOD1) has been investigated to clarify the relationship between mutations in SOD1 and the pathogenesis of amyotrophic lateral sclerosis (ALS). Ala4 -> Val (A4V) and Gly93 -> Ala (G93A) mutants, which are representative ALS-linked SOD1 mutants, have been found to exhibit both the denaturation and the gain of pro-oxidant activity after incubation in the apo-form at a physiological condition of 37 degrees C and pH 7.4 and the rebinding of Cu2+. These characteristics are similar to those previously reported for the His43 -> Arg (H43R) mutant. UV-resonance Raman spectra indicated that the coordination structure of the Cu-binding site catalyzing the oxidation reaction is the same among the denatured A4V, G93A, and H43R. Since wild type SOD1 does not exhibit the denaturation in its apo-form at 37 degrees C and pH 7.4, the instability of the protein structure due to mutation can be considered as a significant factor that induces the denaturation and the subsequent pro -oxidant activity.

• 出版日期2016-11-10