Restored Physiology in Protein-Deficient Yeast by a Small Molecule Channel.
Restored Physiology in Protein-Deficient Yeast by a Small Molecule Channel.
复制标题
DOI：
10.1021/jacs.5b05765
复制
发表时间：
2015-08-19
影响因子：
15
通讯作者：
Burke MD
中科院分区：
文献类型：
--
作者：
Cioffi AG;Hou J;Grillo AS;Diaz KA;Burke MD
蛋白质离子通道的缺陷是许多目前无法治愈的人类疾病的基础。泵和通道的强大网络通常负责从微生物到人类的生物体中特定离子的定向运动。因此，我们质疑缺失蛋白质通道的最低选择性小分子模拟物是否能够与相应的蛋白质离子泵合作以恢复生理学。在这里，我们报告了通过用不完美的小分子模拟物取代缺失的蛋白质离子通道来恢复酵母细胞的生长。我们进一步提供的证据表明，这种容忍不完美的模仿是由于通道形成的小分子和蛋白质离子泵之间的合作。这些结果阐明了一种机制框架，用于寻求小分子替代缺乏蛋白质离子通道，这些离子通道是一系列具有挑战性的人类疾病的基础。
Deficiencies of protein ion channels underlie many currently incurable human diseases. Robust networks of pumps and channels are usually responsible for the directional movement of specific ions in organisms ranging from microbes to humans. We thus questioned whether minimally selective small molecule mimics of missing protein channels might be capable of collaborating with the corresponding protein ion pumps to restore physiology. Here we report vigorous and sustainable restoration of yeast cell growth by replacing missing protein ion channels with imperfect small molecule mimics. We further provide evidence that this tolerance for imperfect mimicry is attributable to collaboration between the channel-forming small molecule and protein ion pumps. These results illuminate a mechanistic framework for pursuing small molecule replacements for deficient protein ion channels that underlie a range of challenging human diseases.