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

点击翻译按钮获取中文摘要

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.