Investigation of Myo-Inositol Oxygenase

这项授予特拉华大学的初学者奖金支持尤金·G·米勒教授的研究。这项研究是对肌醇加氧酶的机理和结构的研究，该酶的催化功能来自蛋白质环境中的非血红素铁。采用的技术包括核磁共振和Moessbauer光谱分析；快速冷冻淬冷法；定点突变；以及包括底物类似物、抑制剂和同位素效应测定在内的稳态和快速动力学研究。除了这些研究中出现的新化学物质外，肌醇加氧酶还具有生理意义。糖尿病动物表现出其活性的显著降低，该酶的抑制会导致迅速的肾功能衰竭。肌醇磷酸盐在细胞信号转导中起着关键作用，而细胞信号转导中的错误是肿瘤发生的媒介。因此，非血红素、含铁酶在维持生命的生物过程中至关重要。

This starter grant award to the University of Delaware supports the research of Professor Eugene G. Mueller. The research is an investigation of the mechanism and structure of the enzyme myo-inositol oxygenase, whose catalytic function arises from a non-heme iron in a protein environment. Techniques employed include nuclear magnetic resonance and Moessbauer spectroscopies; rapid freeze quench methods; site-directed mutagenesis; and steady-state and rapid kinetic studies including substrate analogs, inhibitors, and the determination of isotope effects. In addition to the novel chemistry to emerge from these studies, the enzyme myo-inositol oxygenase is of physiological interest. Diabetic animals show a marked decrease in its acitivity, and inhibition of the enzyme leads to rapid kidney failure. Inositol phosphates play a key role in cellular signaling, errors in which mediate oncogenesis. Thus, non-heme, iron-containing enzymes are vital in life-sustaining biological processes.