Structural and functional characterization of protein-metal interactions.

蛋白质-金属相互作用的结构和功能表征。

• 批准号: RGPIN-2017-05253
• 负责人: Omichinski, James
• 金额: $ 2.48万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=661209
• 关键词: Structural; functional; characterization; protein; metal

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.

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，并且对这些重要相互作用的机制细节进行表征具有相当大的兴趣。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，还有一些金属通常在我们的环境中以高浓度存在，由于它们与细胞蛋白质结合并破坏其正常生物功能的能力而有毒。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在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，我们对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破坏涉及必需金属的正常过程感兴趣。目前，有几个正在进行的研究在实验室检查蛋白质-金属相互作用。例如，我们正在研究常用的降脂药和非甾体抗炎药的硫酯代谢物如何破坏人体细胞中必需的蛋白质-金属相互作用。我们还在研究生物矿化过程中涉及的蛋白质-金属相互作用，这些相互作用在合成银基纳米材料的生产中有潜在的应用，这些纳米材料可用于电子、光学或抗菌剂等各种产品。此外，我们正在研究一些有毒金属，如汞、锡和铅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有效的生物修复系统，利用绿色化学从我们的环境中去除这些剧毒金属。我们提出的蛋白质-金属相互作用的结构和功能研究组合将对我们对一些关键的生化和生物有机机制的理解产生重要影响，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。