Towards [Al.sup.3+]-induced manganese-containing superoxide dismutase inactivation and conformational changes: an integrating study with docking simulations

• Published in: Enzyme research 2011-01
• Main Authors: Yang, Jiang-Liu, Yin, Shang-Jun, Si, Yue-Xiu, Lu, Zhi-Rong, Shao, Xiangrong, Park, Daeui, Chung, Hae Young, Zhou, Hai-Meng, Qian, Guo-Ying, Zhang, Zi-Ping
• Format: Article
• Language: English
• Subjects: Computer simulation; Computer-generated environments; Enzymes; Physiological aspects; Superoxide
• ISSN: 2090-0414
• DOI: 10.4061/2011/307464

Superoxide dismutase (SOD, EC 1.15.1.1) plays an important antioxidant defense role in skins exposed to oxygen. We studied the inhibitory effects of [Al.sup.3+] on the activity and conformation of manganese-containing SOD (Mn-SOD). Mn-SOD was significantly inactivated by [Al.sup.3+] in a dose-dependent manner. The kinetic studies showed that [Al.sup.3+] inactivated Mn-SOD follows the first-order reaction. [Al.sup.3+] increased the degree of secondary structure of Mn-SOD and also disrupted the tertiary structure of Mn-SOD, which directly resulted in enzyme inactivation. We further simulated the docking between Mn-SOD and [Al.sup.3+] (binding energy for Dock 6.3: -14.07 kcal/mol) and suggested that ASP152 and GLU157 residues were predicted to interact with [Al.sup.3+], which are not located in the Mn-contained active site. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of [Al.sup.3+] and allow us to describe a ligand binding via inhibition kinetics combined with the computational prediction.