Trifluoroethanol-Induced Changes in Activity and Conformation of Manganese-Containing Superoxide Dismutase |
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Authors: | Shang-Jun Yin Zhi-Rong Lü Daeui Park Hae Young Chung Jun-Mo Yang Hai-Meng Zhou Guo-Ying Qian Yong-Doo Park |
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Institution: | (1) College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, People’s Republic of China;(2) Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, 314006, People’s Republic of China;(3) Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, 100084, People’s Republic of China;(4) Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, 609-735, South Korea;(5) Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, 135-710, South Korea; |
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Abstract: | Superoxide dismutase (SOD, EC 1.15.1.1) plays an important role in antioxidant defense in organisms exposed to oxygen. However,
there is a lack of research into the regulation of SOD activity and structural changes during folding, especially for SOD
originating from extremophiles. We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation
of manganese-containing SOD (Mn-SOD) from Thermus thermophilus. TFE decreased the degree of secondary structure of Mn-SOD, which directly resulted in enzyme inactivation and disrupted
the tertiary structure of Mn-SOD. The kinetic studies showed that TFE-induced inactivation of Mn-SOD is a first-order reaction
and that the regional Mn-contained active site is very stable compared to the overall structure. We further simulated the
docking between Mn-SOD and TFE (binding energy for Dock 6.3, −9.68 kcal/mol) and predicted that the LEU9, TYR13, and HIS29
residues outside of the active site interact with TFE. Our results provide insight into the inactivation of Mn-SOD during
unfolding in the presence of TFE and allow us to describe ligand binding via inhibition kinetics combined with computational
predictions. |
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