Bioinorganic Chemistry of Nitrogen

氮的生物无机化学 PI研究计划的长期目标是了解生物学如何利用过渡金属来 控制氧化还原活性底物的物种形成，包括反应性或“固定”氮物种（RNS）。反应性 氮物种在生物学中起着重要作用。例如，一氧化氮（NO）是细胞信号传导剂， 调节哺乳动物系统中的血管舒张。在一个单独的背景下，硝酸盐（NO3-）可以取代分子氧 (O2)作为包括人类病原体在内的细菌的细胞呼吸过程中的终端电子受体。 这一建议描述了继续努力，以阐明机制的地球化学氮循环 通过研究金属酶以及相互转化RNS的模型复合物。一个关键的知识差距， 将通过蛋白质组学和酶学来解决氨氧化的方法， 古细菌从羟胺的氧化中获得化学能。有效的酶和 该反应仍然未知。活性引导的纯化和质谱分析将提供这种物质的身份。 用于随后通过光谱学、X射线表征的全局增殖的氮循环蛋白 晶体学和动力学。进一步的工作将探索RNS氧化生物化学中的产物选择性， 血红素P460蛋白，以确定NO如何选择一氧化二氮（N2 O），以区分代谢性 解毒蛋白PI将继续与领先的生物无机化学家合作， 过渡金属如何引发RNS进行氧化或还原，以及如何在这些反应中实现选择性。 这些合作将利用PI在X射线光谱以及其他无机 光谱学这些合作的关键例子包括金属的定点光谱探测 固氮酶FeMo辅因子中的原子、多铜簇还原N2 O的方式以及研究 路易斯酸稳定的RNS的电子结构和反应性已被赋予能够 进行独立于质子转移的氧化还原转化。

Bioinorganic Chemistry of Nitrogen The long-term goal of the PI’s research program is to understand how biology uses transition metals to control the speciation of redox-active substrates including reactive or “fixed” nitrogen species (RNS). Reactive nitrogen species serve vital roles in biology. For example, nitric oxide (NO) is a cellular signaling agent that regulates vasodilation in mammalian systems. In a separate context, nitrate (NO3–) can substitute for dioxygen (O2) as the terminal electron acceptor during cellular respiration by bacteria that include human pathogens. This proposal describes a continuation of efforts to elucidate mechanisms of the biogeochemical nitrogen cycle via the study of metalloenzymes as well as model complexes that interconvert RNS. A key knowledge gap that will be addressed through proteomics and enzymology concerns the means by which ammonia oxidizing archaea derive chemical energy from the oxidation of hydroxylamine. The operative enzyme and the product of this reaction remain unknown. Activity guided purification and mass spectrometry will furnish the identity of this globally proliferated nitrogen cycle protein for subsequent characterization by spectroscopy, X-ray crystallography, and kinetics. Further work will explore product selectivity in RNS oxidation biochemistry by heme P460 proteins to determine how NO is selected over nitrous oxide (N2O) to differentiate metabolic from detoxification proteins. The PI will continue to collaborate with leading bioinorganic chemists to understand how transition metals prime RNS for oxidation or reduction and how selectivity in these reactions is achieved. These collaborations will leverage the PI’s expertise in X-ray spectroscopic as well as in other inorganic spectroscopies. Key examples of these collaborations involve site-selective spectroscopic probing of metal atoms in the FeMo cofactor of nitrogenase, the means by which multicopper clusters reduce N2O, and studying the electronic structures and reactivities of Lewis-acid stabilized RNS that have been rendered capable of undergoing redox transformations independent of proton transfer.