title: Trifluoroethanol-induced changes in activity and conformation of manganese-containing superoxide dismutase.
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.
authors: College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, People's Republic of China.
authors: Shang-Jun
authors: SJ
authors: Yin
authors: Zhi-Rong
authors: ZR
authors: Lü
authors: Daeui
authors: D
authors: Park
authors: Hae Young
authors: HY
authors: Chung
authors: Jun-Mo
authors: JM
authors: Yang
authors: Hai-Meng
authors: HM
authors: Zhou
authors: Guo-Ying
authors: GY
authors: Qian
authors: Yong-Doo
authors: YD
authors: Park
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D004795:Enzyme Stability / Q000187:drug effects; D007700:Kinetics; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000187:drug effects; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000378:metabolism*; D016963:Thermus thermophilus / Q000201:enzymology; D014270:Trifluoroethanol / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D014270:Trifluoroethanol; D013482:Superoxide Dismutase