How the Superoxide Dismutase Protein Specifies the Reactivity of Bound Fe

超氧化物歧化酶蛋白如何确定结合铁的反应性

• 批准号: 0129599
• 负责人: Anne-Frances Miller
• 金额: $ 36.65万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0129599&HistoricalAwards=false
• 关键词: How; Superoxide; Dismutase; Protein; Specifies

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.

Mn-羟氧化物歧化酶和Fe-羟基歧化酶（MNSOD和FESOD）催化一电子氧化并减少超氧化物阴离子（O2--），以分子氧和过氧化氢（O2和H2O2）。这些酶延长了我们的健康寿命，并且与介导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SOD催化活性的决定因素。先前的工作表明，SOD蛋白可以在超过一半的伏特中调整降低中点电位EM，即绑定的Fe2+/3+或Mn2+/3+离子，从而为潜在的化学范围提供了潜在的访问。已提出该蛋白质是通过在保守的活性位点谷氨酰胺和协调的溶剂分子之间通过氢键来实现这一目标的。对天然酶和一些突变体的光谱，结构和热力学研究将阐明该氢键对EM的影响的机理和幅度。此外，将执行MN取代的Fesod的第一个特征，其EM高于900 mV。这项研究将测试金属蛋白中氧化还原调整的合理化学机制。除SOD外，许多金属酶还包括金属离子配体之间的溶剂分子，并且通常，这种溶剂还与蛋白质残基氢键。因此，了解这可以负担得起的氧化还原调整的幅度以及可以操纵它的程度将具有一般适用性。