权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

RUI：量化钙 (II) 和镉 (II) 与 EF 手蛋白相互作用的热力学：了解定义镉离子拟态的因素

基本信息

批准号：
1710347
负责人：
Anne Marie Spuches
金额：
$ 25.2万
依托单位：
East Carolina University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710347&HistoricalAwards=false
关键词：
RUI Quantifying thermodynamics Calcium II

项目摘要

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.

有了这个奖项，化学部门的生命过程化学项目资助了东卡罗莱纳大学的伊丽莎白·史密斯博士，研究镉生物化学的一个很大程度上未被探索的方面。研究人员主要关注镉与含有硫原子作为接触点的蛋白质的相互作用。最近一项对所有可用蛋白质结构的分析发现，镉也更倾向于与蛋白质中的富氧钙位点结合。有趣的是，关于镉与这些蛋白质结合的基本驱动力的数据很少，因此在理解这种相互作用方面存在很大差距。Spuches博士和她的学生的目标是填补关于镉与蛋白质相互作用的知识空白。由美国国家科学基金会生命过程化学计划提供的资金将允许学生在Spuches实验室进行镉与天然钙结合蛋白和模型肽结合的详细热力学和结构研究。将对镉的生物化学的一个很大程度上未被探索的方面进行调查。Spuches实验室将把注意力集中在人类心脏肌钙蛋白C （HcTnC）上，这是一种利用Ca（II）调节心肌收缩的EF-hand蛋白。他们计划在他们的研究中结合使用等温滴定量热法（ITC）、圆二色法（CD）和核磁共振波谱法（113Cd/1H）。拟议的项目将提供Cd（II）和Ca（II）与人心脏肌钙蛋白C和模型肽结合的热力学和结构数据，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httnc和TnI之间随后的蛋白质相互作用。这项工作将使学生受益，让他们学习许多技术，这些技术将为他们在制药和生物技术行业的职业生涯做好准备，或者使他们在攻读博士学位时非常有竞争力。该项目也有可能为北卡罗莱纳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，从这个项目中获得的数据极有可能为镉的毒性提供新的见解。