Hydrogen-bond-mediated tuning of the redox potential of the non-heme Fe site of superoxide dismutase.
Hydrogen-bond-mediated tuning of the redox potential of the non-heme Fe site of superoxide dismutase.
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DOI：
10.1021/ja011220v
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发表时间：
2002-03
影响因子：
15
通讯作者：
Emine Yikilmaz;Juan Xie;T. Brunold;Anne‐Frances Miller
中科院分区：
文献类型：
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作者：
Emine Yikilmaz;Juan Xie;T. Brunold;Anne‐Frances Miller
尽管如此，来自大肠杆菌的含铁超氧化物歧化酶 (FeSOD) 和 MnSOD 的高度同源蛋白对活性位点金属离子发挥着截然不同的氧化还原调节作用 [Vance;米勒·J·Am.化学。苏克。 1998, 120, 461-467;生物化学 2001, 40, 13079-13087]。这被认为是由于蛋白质与金属离子的配位溶剂分子之间的氢键不同，以及配位溶剂的质子化态与金属离子的氧化态之间的紧密耦合。现在，我们提出了与 FeSOD 和 MnSOD 模型结合的 Fe2+ 和 Fe3+ 的密度泛函理论 (DFT) 计算。计算结果支持 MnSOD 中保守的第二球 Gln 在特定地破坏配位 H2O 相对于配位 OH- 的稳定性方面发挥着非常重要的作用，从而不利于金属离子的氧化态。为了测试这些结果，我们将该 Gln 突变为 Glu，Glu 与 Gln 是等排和等电子的，但充当 H 键受体而不是 H 键供体，因此应该会增加 Fe2+ 结合的 H2O 的稳定性。根据计算，Q69E-FeSOD 显示出比野生型 FeSOD 显着更高的还原潜力。因此，我们证明了与配位溶剂的氢键可以对金属离子产生强烈的氧化还原调节。
The highly homologous proteins of Fe-containing superoxide dismutase (FeSOD) and MnSOD from Escherichia coli nonetheless exert very different redox tuning on the active site metal ion [Vance; Miller J. Am. Chem. Soc. 1998, 120, 461-467; Biochemistry 2001, 40, 13079-13087]. This was proposed to stem from different hydrogen bonding between the protein and the metal ion's coordinated solvent molecule, and the tight coupling between the protonation state of coordinated solvent and the oxidation state of the metal ion. We now present density functional theory (DFT) calculations on Fe2+ and Fe3+ bound to models of both FeSOD and MnSOD. The calculations support a very important role for the conserved second sphere Gln in MnSOD in specifically destabilizing coordinated H2O relative to coordinated OH-, and thus disfavouring the oxidized state of the metal ion. To test these results we have mutated this Gln to Glu, which is isosteric and isoelectronic to Gln but functions as an H-bond acceptor instead of an H-bond donor and thus should increase the stability of Fe2+-bound H2O. In accordance with the calculations, Q69E-FeSOD displays a significantly higher reduction potential than wild-type FeSOD. Thus we have demonstrated that hydrogen bonds to coordinated solvent can exert strong redox tuning on a metal ion.