Connections between redox chemistry and catalysis in multiheme peroxidases

化学部的生命过程化学项目将资助波士顿大学的Sean Elliott博士研究能使过氧化氢解毒的细菌酶的蛋白质动力学和调控机制。利用蛋白质电化学、生物化学和结晶学的多学科方法，将通过将血红素辅因子的氧化还原和自旋状态变化与蛋白质结构的构象变化配对，来研究控制氧化还原酶如何开启或关闭反应性的分子决定因素。这样的研究可以从分子水平上理解基于氧化还原的催化调节机制。酶是将一种分子转化为另一种分子的大师。通过这种方式，被称为细胞色素c过氧化物酶(Bccps)的细菌酶能使活性分子过氧化氢解毒，并将其转化为无害的水。像bCCP这样的酶通常也掌握着它们自己的调节，在那里它们要么被打开，要么被关闭。了解酶是如何调节自身活性的，是了解它们如何充当催化剂的关键方面。在这里，将运用广泛的生化、结构、光谱和电化学方法来理解可激活的bCCP的反应性，并阐明什么开启(和关闭)它们的活性的原理。参与这些努力的研究生和本科生将接受多学科培训。该项目将与持续的指导工作相结合，因为学生和PI将发展并作为领导者参加正在进行的一系列生物无机化学研讨会。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Sean Elliott of Boston University to study the protein dynamics and regulatory mechanisms of bacterial enzymes that detoxify hydrogen peroxide. A multi-disciplinary approach making use of protein electrochemistry, biochemistry and crystallography will be used to examine the molecular determinants that govern how a redox enzyme turns on or shuts down reactivity through pairing redox- and spin state- changes of heme cofactors to conformational changes in protein structure. Such studies can provide a molecular level understanding of redox-based mechanisms of the regulation of catalysis. Enzymes are masters of transforming one molecule into another. In this way, bacterial enzymes called cytochrome c peroxidases (bCCPs) detoxify the reactive molecule hydrogen peroxide and transform it into harmless water. Enzymes such as bCCP often also master their own regulation, where they are turned either on or off. Understanding how enzymes regulate their own activity is a critical aspect of understanding how they can act as catalysts. Here, a wide range of biochemical, structural, spectroscopic, and electrochemical approaches will be brought to bear to understand the reactivity of "activatable" bCCP and elucidate the principles of what turns on (and off) their activity. The graduate and undergraduate students involved in these efforts will receive a multi-disciplinary training. This project will be integrated with continued mentoring efforts as students and the PI will develop and participate as leaders in an ongoing series of workshops in bioinorganic chemistry.