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

化学部的生命过程化学项目正在资助布莱恩·F·Shaw使用蛋白质电荷梯来量化七种精心选择的金属蛋白质的净电荷，作为（i）金属化学计量，（ii）金属氧化态，（iii）错义突变和（iv）pH值的函数。这项研究的结果与金属蛋白质的化学和催化的基本理解有关，它们将有助于回答重要的问题，如：金属蛋白的净电荷是否真的有助于其金属离子的氧化还原电位每单位电荷约23 mV？金属蛋白在氧化态之间循环时调节净电荷吗？金属蛋白中可电离基团的协作网络在多大程度上允许它调节其跨pH的净电荷，或者响应错义突变或金属离子的结合？金属蛋白质的净静电荷被用来合理化无数化学过程的速率和自由能变化，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，除了蛋白质不携带净电荷的pH，因为进行这种测量的技术困难。该奖项资助的研究将能够测量金属蛋白的净电荷，从而促进我们对其化学的严格理解。该奖项还资助肖博士的研究小组开发工具，帮助教育工作者向盲人或视力受损的学生教授蛋白质变构。

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.