CAREER: Quantifying the Net Charge of Metalloproteins: a Fundamental but Elusive Property

职业：量化金属蛋白的净电荷：一个基本但难以捉摸的特性

• 批准号: 1352122
• 负责人: Bryan Shaw
• 金额: $ 40.5万
• 依托单位: Baylor University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-15 至 2020-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1352122&HistoricalAwards=false
• 关键词: CAREER; Quantifying; Net; Charge; Metalloproteins

The Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Bryan F. Shaw from Baylor University to use protein charge ladders to quantify the net charge of seven carefully chosen metalloproteins as a function of (i) metal stoichiometry, (ii) metal oxidation state, (iii) missense mutation, and (iv) pH. The results of this research are relevant for the fundamental understanding of the chemistry and catalysis of metalloprotein and they will help answer important questions such as: Does the net charge of a metalloprotein really contribute to the redox potential of its metal ion by ~ 23 mV per unit of charge? Do metalloproteins regulate net charge when cycling between oxidation states? To what degree will the cooperative network of ionizable groups in a metalloprotein allow it to regulate its net charge across pH, or in response to a missense mutation or the binding of a metal ion? The net electrostatic charge of a metalloprotein is used to rationalize the rate and free energy change of a myriad of chemical processes, including electron transfer, molecular recognition, and self-assembly. However, the net charge of nearly all proteins has not been measured at any pH except for the pH at which the protein carries no net electrical charge because of the technical difficulty in making such measurements. The research funded by this award will enable the measurement of the net charge of the metalloproteins and consequently will advance our rigorous understanding of their chemistry. This award is also funding the work of Dr. Shaw's research group to develop tools that will help educators teach protein allostery to blind or visually-impaired students.

化学部生命过程化学计划资助贝勒大学的Bryan F.Shaw博士使用蛋白质电荷梯子来量化精心选择的七种金属蛋白质的净电荷，它们是(I)金属化学计量、(Ii)金属氧化状态、(Iii)错义突变和(Iv)pH的函数。这项研究的结果有助于从根本上理解金属蛋白的化学和催化作用，并将有助于回答一些重要问题，如：金属蛋白的净电荷是否真的对其金属离子的氧化还原电位有贡献，每单位电荷约23 mV？金属蛋白在氧化态之间循环时是否调节净电荷？金属蛋白中可电离基团的合作网络将在多大程度上允许它调节其跨pH的净电荷，或者对错义突变或金属离子的结合做出反应？金属蛋白质的净静电电荷被用来使无数化学过程的速率和自由能变化合理化，包括电子转移、分子识别和自组装。然而，几乎所有蛋白质的净电荷都没有在任何pH下测量过，除了蛋白质不带净电荷的pH，因为这样的测量在技术上是困难的。由该奖项资助的研究将使测量金属蛋白的净电荷成为可能，从而促进我们对其化学的严格理解。该奖项还资助了肖博士的研究小组开发工具，帮助教育工作者向盲人或视障学生教授蛋白质变构。