Presidential Young Investigator Award: Metal Ion Regulationof Gene Expression

根据总统青年研究人员计划，该奖项为生物无机化学领域的研究提供支持。该研究项目的总主题是金属离子在生物系统中扮演的角色。将在两个方面开展研究：探索金属在新型基因调控金属蛋白中的结构和功能作用，以及开发含生物配体的氧活化金属络合物的化学。直接的靶标是金属蛋白，它们在重金属的细胞代谢中发挥关键作用，特别是那些调节基因表达或介导重金属解毒的蛋白。特别是，将关注金属调节蛋白，它们充当金属反应的分子开关，感知金属离子浓度的变化，并调节相关基因的表达。在第二个方面，我们将研究金属-核苷酸络合物对氧的活化。特别令人感兴趣的是ADP和Fe(II)的混合物通过分子氧促进脂质过氧化的机制。将分离和表征铁核苷酸络合物，并探索氧的活化机理及其作为环氧化催化剂的应用。

This award under the Presidential Young Investigator Program provides support for research in the area of bioinorganic chemistry. The general topic of the research project is the roles which metal ions play in biological systems. Research will be pursued on two fronts: exploring the structural and functional roles of metals in novel gene regulatory metalloproteins and developing the chemistry of oxygen activating metal complexes containing biological ligands. The immediate targets are metalloproteins that play key roles in cellular metabolism of heavy metals, particularly those regulating gene expression or mediating heavy metal detoxification. In particular, attention will be given to metalloregulatory proteins which act as metal-responsive molecular switches, sensing changes in metal ion concentrations and adjusting the expression of relevant genes. On the second front the activation of oxygen by metal-nucleotide complexes will be investigated. Of particular interest is the mechanism by which mixtures of ADP and Fe(II) promote lipid peroxidation by molecular oxygen. Iron nucleotide complexes will be isolated and characterized, and the mechanism of activation of oxygen and their utility as epoxidation catalysts will be explored.