Thermodynamics of Metal-Protein Interactions

有了这个奖项，化学部的生命过程化学计划正在资助达特茅斯学院的Dean Wilcox博士，因为他试图获得金属离子与蛋白质结合的新见解。金属通常在自然界中使用，这是由于它们在与蛋白质结合时提供的独特反应性（例如，金属酶）。 蛋白质在生物必需金属（例如，锌、铜、铁），以及有毒的（例如，汞、铅、镉），受到生物体的影响。Wilcox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见解。此外，参与该项目的学生还获得了重要的知识和宝贵的技能，为他们的科学和教育事业，从而提高科学劳动力。这项研究量化了金属离子与蛋白质结合的热力学，以更好地了解金属对蛋白质稳定性的贡献和金属氧化还原性质的蛋白质调节。有关金属-蛋白质相互作用的基本新见解正在从将金属结合热力学与所得金属蛋白质的金属稳定化热力学相关联的研究中获得。 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）。从金属结合的量热测量确定金属蛋白质还原热力学的方法正被应用于选定的金属蛋白质和酶。 这些方法提供了深入了解蛋白质调制的金属还原电位，以及质子转移伴随着减少。正在研究具有较高和较低还原电位的天青蛋白、具有独特Cu（I）配位的多糖单加氧酶和具有两个机械上不同的铜离子的酪胺单加氧酶的几种变体。最后，这种方法正在扩展到铜酶超氧化物歧化酶的研究，以量化的热力学和伴随的质子转移反应。

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.