Yang Jiang-Liu, Yin Shang-Jun, Si Yue-Xiu, Lü Zhi-Rong, Shao Xiangrong, Park Daeui, Chung Hae Young, Zhou Hai-Meng, Qian Guo-Ying, Zhang Zi-Ping
School of Life Science, Ningxia University, Yinchuan 750021, China.
Enzyme Res. 2011;2011:307464. doi: 10.4061/2011/307464. Epub 2011 May 29.
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(3+) on the activity and conformation of manganese-containing SOD (Mn-SOD). Mn-SOD was significantly inactivated by Al(3+) in a dose-dependent manner. The kinetic studies showed that Al(3+) inactivated Mn-SOD follows the first-order reaction. Al(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(3+) (binding energy for Dock 6.3: -14.07 kcal/mol) and suggested that ASP152 and GLU157 residues were predicted to interact with Al(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(3+) and allow us to describe a ligand binding via inhibition kinetics combined with the computational prediction.
超氧化物歧化酶（SOD，EC 1.15.1.1）在暴露于氧气的皮肤中发挥重要的抗氧化防御作用。我们研究了Al(3+)对含锰超氧化物歧化酶（Mn-SOD）活性和构象的抑制作用。Al(3+)以剂量依赖性方式使Mn-SOD显著失活。动力学研究表明，Al(3+)使Mn-SOD失活遵循一级反应。Al(3+)增加了Mn-SOD的二级结构程度，同时破坏了Mn-SOD的三级结构，这直接导致酶失活。我们进一步模拟了Mn-SOD与Al(3+)之间的对接（Dock 6.3的结合能：-14.07 kcal/mol），并表明预测ASP152和GLU157残基与Al(3+)相互作用，它们并不位于含锰活性位点。我们的结果为在Al(3+)存在下Mn-SOD解折叠过程中的失活提供了见解，并使我们能够通过抑制动力学结合计算预测来描述配体结合。
