EXAFS STUDIES OF NONHEME IRON ENZYMES AND MODEL COMPOUNDS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 非血红素铁酶通过激活分子氧催化广泛的重要代谢转化。在这些酶的提出的机制中，分子氧每次还原一个电子，依次得到铁（III）-超氧、铁（III）-过氧或氢过氧和铁（IV）-氧代中间体。深入了解这些机制的一个重要策略是通过捕获和表征这些中间体，无论是在酶的周转过程中，还是在这些酶的功能模型。X射线吸收光谱在确定这些被捕获的中间体的结构中发挥了关键作用。在接下来的两年SSRL期间，我们将研究在CD 4存在下的MMO中间体P和Q，以及感兴趣的高价铁-氧代中间体，包括第一个铁（V）-氧代物种和新的二铁（III，IV）和二铁（IV）中间体，其中一些将通过电化学氧化产生。对DAOCS（将青霉素转化为头孢菌素的2-酮戊二酸依赖性酶）的研究也将启动，以解决由意外结晶学结果引起的机制问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nonheme iron enzymes catalyze a broad range of metabolically important transformations by activating dioxygen. In the proposed mechanisms of those enzymes, dioxygen is reduced one electron at a time to afford in turn iron(III)-superoxo, iron(III)-peroxo or hydroperoxo, and iron(IV)-oxo intermediates. An important strategy to gain insight into these mechanisms is by trapping and characterizing such intermediates either during enzyme turnover or in functional models of such enzymes. X-ray absorption spectroscopy has played a key role in establishing the structures of these trapped intermediates. In the following SSRL two-year period, we will study MMO intermediates P and Q in the presence of CD4, as well as high-valent iron-oxo intermediates of interest, including the first iron(V)-oxo species and new diiron(III,IV) and diiron(IV) intermediates, some of which will be generated by electrochemical oxidation. Studies on DAOCS, the 2-oxoglutarate-dependent enzyme that converts penicillin to cephalosporin, will also be initiated to address a mechanistic question posed by an unexpected crystallographic result.