Jackson Timothy A, Brunold Thomas C
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Acc Chem Res. 2004 Jul;37(7):461-70. doi: 10.1021/ar030272h.
Superoxide dismutases (SODs) are metalloenzymes that protect aerobic organisms from oxidative damage mediated by the superoxide radical. While the Fe- and Mn-dependent SODs from E. coli possess virtually identical protein folds and active-site geometries, they are strictly metal specific. To explore the origin of this extraordinary metal-ion specificity and to elucidate the mechanisms by which these enzymes tune the geometric and electronic properties, and thus the reactivity, of their active-site metal ions, we utilized a combination of spectroscopic and computational methods to study the native enzymes, their metal-substituted derivatives, and several mutant proteins. Results from our research described in this Account reveal that second-sphere residues are critically involved in controlling both thermodynamic and kinetic properties of the Fe- and MnSOD active sites.
超氧化物歧化酶（SODs）是金属酶，可保护需氧生物免受超氧阴离子介导的氧化损伤。虽然来自大肠杆菌的铁依赖性和锰依赖性SOD具有几乎相同的蛋白质折叠和活性位点几何结构，但它们对金属具有严格的特异性。为了探究这种非凡的金属离子特异性的起源，并阐明这些酶调节其活性位点金属离子的几何和电子性质以及反应活性的机制，我们结合了光谱学和计算方法来研究天然酶、它们的金属取代衍生物以及几种突变蛋白。本综述中描述的我们的研究结果表明，第二配位层残基在控制铁和锰超氧化物歧化酶活性位点的热力学和动力学性质方面起着关键作用。
