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如何利用过渡金属 控制氧化还原活性底物的形态，包括活性或固定的氮物种(RN)。反应性 氮物种在生物学中起着至关重要的作用。例如，一氧化氮(NO)是一种细胞信号转导因子， 调节哺乳动物系统中的血管扩张。在另一种情况下，硝酸盐(NO3-)可以替代氧气 (O2)作为包括人类病原体在内的细菌在细胞呼吸过程中的终端电子受体。 这一建议描述了阐明生物地球化学氮循环机制的持续努力。 通过对金属酶以及相互转化RNS的模型络合物的研究。关键的知识差距 将通过蛋白质组学和酶学研究氨氧化的方式来解决 古生菌从羟胺的氧化中获得化学能。该操作酶及其产物 这一反应仍不得而知。活性导向纯化和质谱分析将提供这一特征。 全球增殖型氮循环蛋白，用于后续光谱分析、X射线分析 结晶学和动力学。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，以确定如何选择NO而不是一氧化二氮(N2O)来区分代谢 解毒蛋白。PI将继续与领先的生物无机化学家合作，以了解 过渡金属如何使RN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射线光谱学以及其他无机材料方面的专业知识 分光镜。这些合作的关键例子包括对金属的现场选择性光谱探测 固氮酶的FeMo辅助因子中的原子，多铜簇合物还原N2O的方法，并研究 路易斯酸稳定的RNS的电子结构和反应性已经被呈现为能够 经历不依赖于质子转移的氧化还原转变。

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.