How the Superoxide Dismutase Protein Specifies the Reactivity of Bound Fe

锰超氧化物歧化酶和铁超氧化物歧化酶(MnSOD和FeSOD)催化超氧阴离子(O2-)交替单电子氧化还原为分子氧和过氧化氢(O2和H2O2)。这些酶延长了我们的健康寿命，并与调节有毒废物降解和抗生素合成的酶密切相关。这项研究试图了解决定超氧化物歧化酶催化活性的因素。以前的工作表明，SOD蛋白可以调节结合的Fe2+/3+或Mn2+/3+离子的还原中点电位Em超过0.5伏，从而提供了进入广泛化学范围的潜在途径。该蛋白质被认为是通过保守的活性部位谷氨酰胺和配位溶剂分子之间的氢键来实现这一点的。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对Em的影响的机制和大小。此外，还将首次对Em大于900 mV的锰取代的FeSOD进行表征。这项研究将测试金属蛋白氧化还原调节的合理化学机制。除了超氧化物歧化酶以外，许多金属酶还包括金属离子配体中的一种溶剂分子，通常这种溶剂也会与蛋白质残基形成氢键。因此，对氧化还原调谐的大小以及可以操纵的程度的理解将具有普遍的适用性。

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.