Thermodynamics of Metal-Protein Interactions

金属-蛋白质相互作用的热力学

• 批准号: 1609553
• 负责人: Dean Wilcox
• 金额: $ 40.03万
• 依托单位: Dartmouth College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1609553&HistoricalAwards=false
• 关键词: Thermodynamics; Metal; Protein; Interactions

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Dean Wilcox from Dartmouth College as he seeks to obtain new insights into the binding of metal ions to proteins. Metals are often used in Nature due to the unique reactivity they provide when they are bound to a protein (e.g., metalloenzymes). Proteins play key roles in the uptake, transport, use and excretion of biologically essential metals (e.g., zinc, copper, iron), as well as toxic ones (e.g., mercury, lead, cadmium), by living organisms. Dr. Wilcox's studies are providing fundamental insights into how proteins interact with metal ions in the cell. Additionally, students working on this project are gaining important knowledge and valuable skills for their careers in science and education, thereby enhancing the scientific workforce.This research quantifies the thermodynamics of metal ions binding to proteins in order to provide a better understanding of metal contributions to protein stability and protein modulation of metal redox properties. Fundamental new insights about metal-protein interactions are being obtained from studies that correlate metal-binding thermodynamics to the thermodynamics of metal stabilization of the resulting metalloprotein. The Wilcox group quantifies solvent contributions to metal-binding thermodynamics, and determine metal contributions (bonding, electrostatics) to metalloproteins binding to DNA. A method that determines the metalloprotein reduction thermodynamics from calorimetric measurements of metal binding is being applied to selected metalloproteins and enzymes. These methods provide insight into protein modulation of the metal reduction potential, as well as proton transfer accompanying reduction. Several variants of azurin with higher and lower reduction potentials, polysaccharide monooxygenase, which has a unique Cu(I) coordination, and tyramine-monooxygenase, which has two mechanistically-distinct copper ions are being studied. Finally, this method is being extended to studies of the copper enzyme superoxide dismutase to quantify the thermodynamics and accompanying proton transfer reactions.

通过这个奖项，化学部生命过程化学项目资助了达特茅斯学院的迪恩·威尔科克斯博士，他正在寻求获得金属离子与蛋白质结合的新见解。金属在自然界中经常被使用，因为当它们与蛋白质结合时，它们提供了独特的反应性（例如，金属酶）。蛋白质在生物体摄取、运输、使用和排泄生物必需金属（如锌、铜、铁）以及有毒金属（如汞、铅、镉）方面发挥关键作用。威尔科克斯博士的研究为蛋白质如何与细胞中的金属离子相互作用提供了基本的见解。此外，参与该项目的学生还可以获得重要的知识和宝贵的技能，为他们在科学和教育领域的职业发展提供帮助，从而增强科学队伍的实力。本研究量化了金属离子与蛋白质结合的热力学，以便更好地理解金属对蛋白质稳定性的贡献以及蛋白质对金属氧化还原性质的调节。从金属结合热力学与金属蛋白稳定热力学的相关研究中，获得了关于金属-蛋白质相互作用的基本新见解。Wilcox小组量化了溶剂对金属结合热力学的贡献，并确定了金属对金属蛋白与DNA结合的贡献（键合，静电）。一种通过金属结合的量热测量来确定金属蛋白还原热力学的方法被应用于选定的金属蛋白和酶。这些方法提供了深入了解蛋白质对金属还原电位的调节，以及伴随还原的质子转移。目前正在研究几种具有高还原电位和低还原电位的蓝蛋白变体，具有独特铜(I)配位的多糖单加氧酶和具有两种机械不同铜离子的酪胺-单加氧酶。最后，将该方法推广到铜酶超氧化物歧化酶的研究中，量化其热力学和伴随的质子转移反应。