title: The binding characteristics of isoniazid with copper-zinc superoxide dismutase and its effect on enzymatic activity.
abstract: BACKGROUND
  Isoniazid (INH) is front-line anti-tuberculosis (TB) drugs, which are usually prescribed to TB patients for a total period of 6 months. Antituberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction of TB treatment. It is reported that INH-induced hepatotoxicity is associated with oxidative stress. Superoxide dismutase (SOD, EC 1.15.1.1) is the key enzyme for the protection of oxidative stress, which catalyzes the removal of superoxide radical anion, thereby raising the need to better understand the interaction between INH and SOD.
  
  
  RESULTS
  The experimental results showed that the fluorescence intensity of Cu/Zn-SOD regularly decreased owing to form a 1:1 INH-SOD complex. According to the corresponding association constants (K SV) between INH and SOD obtained from Stern-Volmer plot, it is shown that values of K A are 1.01 × 10(4), 5.31 × 10(3), 3.33 × 10(3), 2.20 × 10(3) L · mol(-1) at four different temperatures, respectively. The binding constants, binding sites and the corresponding thermodynamic parameters ((Δ) H, (Δ) G and (Δ) S) were calculated. A value of 3.93 nm for the average distance between INH and chromophore of Cu/Zn-SOD was derived from Förster theory of non-radiation energy transfer. The conformational investigation showed that the presence of INH resulted in the microenvironment and conformational changes of Cu/Zn-SOD. In addition, Effects of INH on superoxide dismutase activity was examined.
  
  
  CONCLUSIONS
  The results show that the hydrogen bonding and van der Waals forces play major roles in stabilizing the 1:1 INH-SOD complex. After addition of INH during the range of the experiment, the conformation and microenvironment of Cu/Zn-SOD are changed, but the activity of Cu/Zn-SOD is not changed.
authors.affiliation: College of Chemistry and Chemical Engineering, Fuyang Normal College, Fuyang 236041, People's Republic of China.
authors.forename: Nana
authors.initials: N
authors.lastname: Du
authors.affiliation: College of Chemistry and Chemical Engineering, Fuyang Normal College, Fuyang 236041, People's Republic of China ; College of Chemistry and Chemical Engineering, Anhui University, Hefei 230039, People's Republic of China.
authors.forename: Liangquan
authors.initials: L
authors.lastname: Sheng
authors.affiliation: College of Chemistry and Chemical Engineering, Fuyang Normal College, Fuyang 236041, People's Republic of China.
authors.forename: Zhaodi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Fuyang Normal College, Fuyang 236041, People's Republic of China ; College of Chemistry and Chemical Engineering, Anhui University, Hefei 230039, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Hu
authors.affiliation: College of Chemistry and Chemical Engineering, Fuyang Normal College, Fuyang 236041, People's Republic of China.
authors.forename: Huajie
authors.initials: H
authors.lastname: Xu
authors.affiliation: College of Chemistry and Chemical Engineering, Fuyang Normal College, Fuyang 236041, People's Republic of China.
authors.forename: Shuisheng
authors.initials: S
authors.lastname: Chen
keywords: Antioxidation; Interaction; Isoniazid; Superoxide dismutase