RUI: Quantifying the thermodynamics of Calcium(II) and Cadmium(II) interactions with EF-hand proteins: Understanding the factors that define Cadmium ion mimicry

有了这个奖项，化学部的生命过程化学项目将资助来自东卡罗来纳大学的伊丽莎白·史密斯博士研究镉生物化学中一个基本上未被探索的方面。研究人员主要关注镉与含有硫原子的蛋白质之间的相互作用。最近对所有可用的蛋白质结构的分析发现，镉也更喜欢与蛋白质中富氧的钙结合。有趣的是，关于镉与这些蛋白质结合的基本驱动力的数据非常少，因此造成了对这种相互作用的理解上的巨大差距。斯普切斯博士和她的学生们的目标是填补镉与蛋白质相互作用方面的知识空白。由NSF生命过程化学项目提供的资金将允许SPUCHES实验室的学生对镉与天然钙结合蛋白和模型肽结合的热力学和结构进行详细的研究。将对镉的生物化学中一个很大程度上尚未探索的方面进行调查。斯普奇斯实验室将把他们的注意力集中在人类心肌肌钙蛋白C(HcTnC)上，这是一种EF-Hand蛋白，利用Ca(II)来调节心肌收缩。他们计划在他们的研究中结合使用等温滴定热法(ITC)、圆二色谱(CD)和核磁共振光谱(113Cd/1H)。这项拟议的项目将提供Cd(II)和Ca(II)与人心肌肌钙蛋白C结合的热力学和结构数据以及模型肽，从而揭示Cd(II)和Ca(II)与EF-Hand蛋白结合的差异。该项目还将探索在Cd(II)存在下HcTnC和TnI之间的后续蛋白质相互作用。这项工作将使学生受益，因为他们可以学习多种技术，为他们在制药和生物技术行业的职业生涯做准备，或者使他们在博士课程中具有很强的竞争力。该项目还有可能为北卡罗来纳州东部提供高技能的研究人员，从而对该地区的经济增长产生积极影响。最重要的是，从该项目获得的数据很可能为镉毒性提供新的见解。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Elizabeth Smith from Eastern Carolina University to investigate a largely unexplored aspect of the biological chemistry of cadmium. Researchers have mainly focused on cadmium interactions with proteins that contain sulfur atoms as a point of contact. A recent analysis of all available protein structures found that cadmium prefers binding to oxygen rich calcium sites in proteins as well. Interestingly, there is very little data regarding the fundamental driving force for cadmium binding to these proteins therefore creating a large gap in the understanding of such interactions. It is the goal of Dr. Spuches and her students to fill this gap in knowledge regarding cadmium interactions with proteins. Funds provided by the NSF Chemistry of Life Processes Program will allow students in the Spuches lab to conduct a detailed thermodynamic and structural investigation of cadmium binding to natively calcium binding proteins and model peptides. There will be an investigation of a largely unexplored aspect of the biological chemistry of cadmium. The Spuches lab will focus their attention on human cardiac troponin C (HcTnC), an EF-hand protein that utilizes Ca(II) to regulate cardiac muscle contraction. They plan to use a combination of isothermal titration calorimetry (ITC), circular dichroism (CD), and NMR spectroscopy (113Cd/1H) in their studies. The proposed project will provide thermodynamic and structural data on Cd(II) and Ca(II) binding to human cardiac Troponin C and model peptides thereby exposing the differences between Cd(II) and Ca(II) binding to EF-hand proteins. The project will also explore subsequent protein interactions between HcTnC and TnI in the presence of Cd(II). This work will benefit students by allowing them to learn a multitude of techniques that will prepare them for careers in the pharmaceutical and biotechnology industries or make them very competitive for PhD programs. The project also has the possibility to provide Eastern North Carolina with highly skilled researchers thus positively impacting economic growth in the region. Most importantly, the data obtained from this project are highly likely to provide new insights into cadmium toxicity.