How the Superoxide Dismutase Protein Specifies the Reactivity of Bound Fe

Mn-超氧化物歧化酶和Fe-超氧化物歧化酶（MnSOD和FeSOD）催化超氧阴离子（O2 -）交替单电子氧化和还原为分子氧和过氧化氢（O2和H2 O2）。这些酶延长了我们的健康寿命，并且与介导有毒废物降解和抗生素合成的酶密切相关。本研究旨在了解SOD催化活性的决定因素。先前的工作已经表明，SOD蛋白可以在超过半伏的范围内调节结合的Fe 2 +/3+或Mn 2 +/3+离子的还原中点电位Em，从而提供了对广泛化学的潜在访问。已经提出蛋白质通过保守的活性位点谷氨酰胺和配位溶剂分子之间的氢键来实现这一点。对天然酶和一些突变体的光谱、结构和热力学研究将阐明这种氢键作用对Em的影响的机制和大小。此外，Mn取代的FeSOD，其Em高于900 mV，将进行首次表征。这项研究将测试一个合理的，化学机制的氧化还原调整金属蛋白质。除了SOD之外，许多金属酶在金属离子配体中包括溶剂分子，并且通常该溶剂也与蛋白质残基氢键结合。因此，对于这可以提供的氧化还原调节的幅度以及其可以被操纵的程度的理解将具有普遍适用性。

Mn-superoxide dismutase and Fe-superoxide dismutase (MnSOD and FeSOD) catalize alternating one-electron oxidation and reduction of the superoxide anion (O2 -), to molecular oxygen and hydrogen peroxide (O2 and H2O2). These enzymes extend our healthy life, and are closely related to enzymes that mediate degradation of toxic wastes, and synthesis of antibiotics. This research seeks to understand the determinants of SOD's catalytic activity. Previous work has shown that the SOD proteins can tune the reduction midpoint potential, Em , of the bound Fe2+/3+ or Mn2+/3+ ion over more than half a volt, thus providing potential access to a wide range of chemistry. The protein has been proposed to achieve this via hydrogen bonding between a conserved active site glutamine and a coordinated solvent molecule. The spectroscopic, structural and thermodynamic studies, on native enzymes and a few mutants, will elucidate the mechanism and magnitude of this hydrogen bonding's effect on the Em. In addition, the first characterizations of Mn-substituted FeSOD, whose Em is higher than 900 mV, will be carried out. This research will test a rational, chemical mechanism for redox tuning in metalloproteins. Many metalloenzymes besides SOD include a solvent molecule among the metal ion ligands, and as a rule this solvent also hydrogen bonds with protein residues. Thus, understanding gained as to the magnitude of redox tuning this can afford, and the extent to which it can be manipulated, will have general applicability.