Heme protein catalysis and the biocoordination chemistry of HNO

生命过程化学(CLP)项目的这一奖项支持贝勒大学的Patrick Farmer教授在生物NOx催化方面的工作，最近的重点是金属蛋白的氮氧基(HNO)加合物的生成和反应。氮氧化物中间体参与控制动植物氮代谢的酶的催化循环。以前的工作已经确定了还原途径中的几个不同步骤，包括金属结合HNO中间体的形成。Farmer实验室已经证明，许多亚铁血红素蛋白，如肌红蛋白和血红蛋白，可以有效地捕获HNO，形成稳定的HNO加合物。与氧合肌球蛋白一样，这些HNO络合物是低自旋d6和抗磁性的；它们已经通过不同的光谱和分析技术进行了很好的表征，包括核磁共振(核磁共振)、质谱学(MS)和X射线吸收光谱(XAS)。新的项目继续探索HNO的生物配位化学，包括新的非血红素酶的“氮氧基”加合物和模型络合物。利用O2对黄酮醇进行化学修饰的酶quercetinase，已被证明在HNO存在的情况下发生转化，产生结合了氮氧基原子的产物。经典配位化学、分子生物学和物理表征技术的结合为研究生和本科生提供了广泛的培训范围。一个部门的核磁共振仪器将通过高级仪器研讨会升级用于推广到来自较小地区大学的大学生，该研讨会在2009年接待了来自10个不同学校的22名学生和8名教职员工，其中大多数来自代表性不足的群体。该奖项的目的是从无机的角度解决金属蛋白反应的机械方面，即生物氮基新陈代谢的无机化学。当HNO与O2结合蛋白反应时，Farmer教授和他的团队假设它应该与已知的结合氧的金属位置形成稳定的络合物。这一假说已经导致了一种以前未知的酶反应的发现。最终，这些研究将在理解非碳温室气体产生的化学基础的基础上，对现代农业的全球影响产生影响。

This award in the Chemistry of Life Processes (CLP) program supports work by Professor Patrick Farmer at Baylor University on biological NOx catalysis, with a recent focus on the generation and reactivity of nitroxyl (HNO) adducts of metalloproteins. NOx intermediates are involved in the catalytic cycles of enzymes that control nitrogen-based metabolism in plants and animals. Previous work has identified several distinct steps in reductive pathways, including the formation of metal-bound HNO intermediates. The Farmer lab has demonstrated that many ferrous heme proteins like myoglobin and hemoglobin trap free HNO efficiently to form stable HNO adducts. Like oxymyoglobin, these HNO complexes are low spin d6 and diamagnetic; they have been well characterized by different spectroscopic and analytical techniques, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and X-ray Absorption Spectroscopy (XAS). New projects continue the exploration of the bio-coordination chemistry of HNO, including new "nitroxyl" adducts of non-heme enzymes and model complexes. The enzyme quercetinase which utilizes O2 to chemically modify flavonols, has been shown to turnover in the presence of HNO, generating products that incorporate the atoms of nitroxyl. The combination of classical coordination chemistry, molecular biology and physical characterization techniques provides a wide breadth of training for both graduate and undergraduate students. A departmental NMR instrument will be upgraded for use in outreach to college students from smaller regional colleges through the Advanced Instrumentation Workshop, which hosted 22 students and 8 faculty members from 10 different schools in 2009, the majority from underrepresented groups.The intent of this award is to address mechanistic aspects of metalloprotein reactivity from an inorganic perspective, i.e., the inorganic chemistry that underlies biological nitrogen-based metabolism. As HNO reacts with O2-binding proteins, Professor Farmer and his team hypothesize that it should form stable complexes with metal sites that are known to bind oxygen. This hypothesis has already led to identification of a previously unknown enzymatic reaction. Ultimately, these studies will have implications for the global effects of modern agriculture, based on understanding the chemical basis for the generation of non-carbon greenhouse gases.