Structural and functional characterization of protein-metal interactions.

金属-蛋白质相互作用在调节许多生物过程中起着至关重要的作用，人们对描述这些重要相互作用的机制细节很感兴趣。例如，钙、铜、铁和锌等金属通过与特定蛋白质的特定相互作用发挥关键的生物学作用，这些相互作用对包括人类、细菌和植物在内的许多生物的生存至关重要。除了这些必需金属外，环境中常见的高浓度金属也是有毒的，因为它们能够与细胞蛋白质结合并破坏其正常的生物功能。对我们的健康和环境构成严重威胁的有毒金属包括汞、铅、锡、镉和砷。在过去的25年里，我的实验室一直在研究蛋白质与必需金属和有毒金属的相互作用。我们研究计划的长期目标是从结构和功能上表征蛋白质-金属相互作用，包括必需金属和有毒金属。特别是，我们感兴趣的是必需金属如何帮助蛋白质折叠成其功能构象，以及有毒金属如何扰乱涉及必需金属的正常过程。目前，实验室中正在进行几项研究，以检验蛋白质与金属的相互作用。例如，我们正在研究常用降脂药物和非类固醇抗炎药的硫酯代谢物如何扰乱人类细胞中基本的蛋白质-金属相互作用。我们还在研究生物矿化中涉及的蛋白质-金属相互作用，这些相互作用可能应用于合成银基纳米材料的生产，这些纳米材料用于电子、光学或作为抗菌剂等各种产品。此外，我们正在研究汞、锡和铅等一些有毒金属与细菌蛋白质的相互作用，以确定如何更好地利用这些细菌蛋白质来开发高效的生物修复系统，利用绿色化学将这些剧毒金属从我们的环境中去除。我们正在进行的关于蛋白质-金属相互作用的结构和功能研究的拟议组合将对我们理解一些关键的生化和生物有机机制产生重要影响，这些机制将应用于有毒金属修复、纳米材料生产以及我们对常用药物相关毒性的理解。

Metal-protein interactions play crucial roles in regulating a number of biological processes, and there is considerable interest in characterizing the mechanistic details of these important interactions. For example, metals such as calcium, copper, iron and zinc play key biological roles through specific interactions with select proteins, and these interactions are essential for the survival of many organisms including humans, bacteria and plants. In addition to these essential metals, there are also metals commonly present in high concentrations in our environment that are toxic by virtue of their ability to associate with cellular proteins and disrupt their normal biological functions. Toxic metals that pose a serious threat to both our health and environment include mercury, lead, tin, cadmium and arsenic. For the last twenty-five years, my laboratory has been characterizing the interaction of proteins with both essential and toxic metals. The long-term objectives of our research program are to structurally and functionally characterize protein-metal interactions involving both essential and toxic metals. In particular, we are interested in how essential metals help proteins fold into their functional conformation as well as how toxic metals can disrupt the normal processes involving essential metals. Currently, there are several ongoing investigations in the laboratory examining protein-metal interactions. For example, we are examining how thioester metabolites of commonly used lipid lowering and non-steroidal anti-inflammatory drugs disrupt essential protein-metal interactions in human cells. We are also examining protein-metal interactions involved in biomineralization that have potential applications to the production of synthetic silver-based nanomaterials for use in such diverse products as electronics, optics or as antimicrobial agents. In addition, we are examining the interaction of a number of toxic metals such as mercury, tin and lead with bacterial proteins to determine how these bacterial proteins might be better used to develop efficient bioremediation systems that utilize green chemistry for removing these extremely toxic metals from our environment. The proposed combination of structural and functional studies on protein-metal interactions that we undertaking will have an important impact on our understanding of a number of crucial biochemical and bioorganic mechanisms that will have applications to toxic metal remediation, nanomaterial production as well as our understanding of toxicities associated with commonly used drug agents.