Amino acid networks in enzyme catalysis

该项目旨在了解和操纵酶功能所必需的蛋白质机制，这将有助于开发对工业和生物技术应用至关重要的下一代酶。酶加速和控制对生命至关重要的化学反应，许多酶已在广泛的化学工业中得到应用。酶可以被想象成纳米级的机器，它具有对其功能很重要的运动部件。通过学习这些机械运动的基本原理，研究人员将能够更好地设计酶，以在所需条件下加速所需的化学反应。这项研究还将为历史上代表性不足的群体的学生提供科学培训机会。该项目将把初中、高中和本科生融入研究和推广活动中，为年龄较大的学生提供独特的指导机会，并培养多样化和包容性的科学研究环境。酶的三维结构通过非共价相互作用网络连接在一起。这项研究将揭示对酶功能重要的相互作用网络，以了解这些网络如何引导酶的内部运动。将要研究的模型系统是色氨酸合酶，其α和β亚基催化色氨酸氨基酸生物合成的最后两个步骤。相互作用网络被认为对单个酶的功能和亚基间的通讯都很重要。该网络将通过蛋白质核磁共振（NMR）光谱，分子动力学（MD）模拟和蛋白质序列的生物信息学分析相结合来描绘。该项目还将通过诱变和共价修饰靶向表面暴露的网络氨基酸残基来操纵这些网络和酶功能。该项目旨在开发酶中工程相互作用网络的一般规则。

This project aims to understand and manipulate the protein machinery necessary for enzyme function, which will facilitate the development of next-generation enzymes important for industrial and biotechnological applications. Enzymes speed up and control the chemical reactions important for life, and many enzymes have found uses in a wide-range of chemical industries. Enzymes can be envisioned as nanoscale machines, which have moving parts important for their function. By learning the principles underlying these mechanical motions, researchers will be able to better engineer enzymes to speed up desired chemical reactions under desired conditions. This research will also provide scientific training opportunities to students from historically underrepresented groups. This project will integrate middle school, high school and undergraduate students into research and outreach activities, allowing unique mentoring opportunities for older students and fostering a diverse and inclusive scientific research environment.The three-dimensional structures of enzymes are held together by networks of noncovalent interactions. This research will uncover the interaction networks important for enzyme function to provide an understanding of how these networks guide the internal motions of enzymes. The model system that will be studied is tryptophan synthase, whose alpha and beta subunits catalyze the final two steps in tryptophan amino acid biosynthesis. The interaction networks are proposed to be important both for individual enzyme function and inter-subunit communication. The networks will be delineated by a combination of protein nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations and bioinformatics analyses of protein sequences. The project will also manipulate these networks and enzyme function by targeting surface-exposed, network amino acid residues through mutagenesis and covalent modification. The project aims to develop general rules for engineering interaction networks in enzymes.