Abstract
Superoxide dismutase (SOD, EC 1.15.1.1) plays an important antioxidant defense role in organisms exposed to oxygen. Copper- and zinc-containing SOD (Cu/Zn-SOD) catalysis and the change in folding behavior of this enzyme in response to inactivators are therefore of interest. We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of a Cu/Zn-SOD from Bos taurus. We found that TFE inactivated the enzyme and disrupted the tertiary and secondary structures of Cu/Zn-SOD. Kinetic studies showed that TFE-induced inactivation of Cu/Zn-SOD follows first-order reaction kinetics and that TFE binding sites are distinct from the copper- and zinc-containing active site. These structural changes occurred prior to enzyme activity loss. A computational docking simulation of Cu/Zn-SOD and TFE (binding energy of Dock 6.3: -11.52 kcal/mol) suggested that THR37, ASP40, and GLU119, which are located near the active site, interact with TFE. Evaluation of the ligand binding kinetics of Cu/Zn-SOD during unfolding in the presence of TFE combined with computational prediction allowed us to gain insight into the inactivation of Cu/Zn-SOD.
Keywords: Active site, docking simulation, folding, inactivation kinetics, superoxide dismutase, trifluoroethanolActive site, docking simulation, folding, inactivation kinetics, superoxide dismutase, trifluoroethanol
Protein & Peptide Letters
Title: Trifluoroethanol-induced Activity and Structural Changes in Bos taurus Copper- and Zinc-containing Superoxide Dismutase
Volume: 18 Issue: 7
Author(s): Long Shi, Yong Xia, Ming Zhang, Shang-Jun Yin, Yue-Xiu Si, Guo-Ying Qian, Zhi-Rong Lu, Hai-Meng Zhou, Daeui Park, Hae Young Chung, Fei Zou and Yong-Doo Park
Affiliation:
Keywords: Active site, docking simulation, folding, inactivation kinetics, superoxide dismutase, trifluoroethanolActive site, docking simulation, folding, inactivation kinetics, superoxide dismutase, trifluoroethanol
Abstract: Superoxide dismutase (SOD, EC 1.15.1.1) plays an important antioxidant defense role in organisms exposed to oxygen. Copper- and zinc-containing SOD (Cu/Zn-SOD) catalysis and the change in folding behavior of this enzyme in response to inactivators are therefore of interest. We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of a Cu/Zn-SOD from Bos taurus. We found that TFE inactivated the enzyme and disrupted the tertiary and secondary structures of Cu/Zn-SOD. Kinetic studies showed that TFE-induced inactivation of Cu/Zn-SOD follows first-order reaction kinetics and that TFE binding sites are distinct from the copper- and zinc-containing active site. These structural changes occurred prior to enzyme activity loss. A computational docking simulation of Cu/Zn-SOD and TFE (binding energy of Dock 6.3: -11.52 kcal/mol) suggested that THR37, ASP40, and GLU119, which are located near the active site, interact with TFE. Evaluation of the ligand binding kinetics of Cu/Zn-SOD during unfolding in the presence of TFE combined with computational prediction allowed us to gain insight into the inactivation of Cu/Zn-SOD.
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Shi Long, Xia Yong, Zhang Ming, Yin Shang-Jun, Si Yue-Xiu, Qian Guo-Ying, Lu Zhi-Rong, Zhou Hai-Meng, Park Daeui, Chung Hae Young, Zou Fei and Park Yong-Doo, Trifluoroethanol-induced Activity and Structural Changes in Bos taurus Copper- and Zinc-containing Superoxide Dismutase, Protein & Peptide Letters 2011; 18 (7) . https://dx.doi.org/10.2174/092986611795446021
DOI https://dx.doi.org/10.2174/092986611795446021 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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