专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明申请

WO2004065363A2 COMPUTATIONAL DESIGN OF A WATER-SOLUBLE ANALOG OF A PROTEIN, SUCH AS PHOSPHOLAMBAN AND POTASSIUM CHANNEL KCSA 审中-公开
标题翻译：蛋白质水溶性模拟物的计算设计，如磷酰胺和钾通道KCSA
公开(公告)号：WO2004065363A2
公开(公告)日：2004-08-05
申请号：PCT/US2004/001317
申请日：2004-01-21
申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA , SAVEN, Jeffrery, G. , DEGRADO, William, F. , SLOVIC, Avram, M. , SUMMA, Christopher, M. , KONO, Hidetoshi
发明人： SAVEN, Jeffrery, G. , DEGRADO, William, F. , SLOVIC, Avram, M. , SUMMA, Christopher, M. , KONO, Hidetoshi
IPC分类号： C07D
CPC分类号： G06F19/16 , G06F19/18
摘要： Membrane proteins and water-soluble proteins share a similar core. This similarity suggests that it should be possible to water-solubilize membrane proteins by mutating only their lipid-exposed residues. Computational tools and methods are disclosed herein that can be used to design water-soluble variants of helical membrane proteins, using the pentameric phospholamban (PLB) and potassium channel KcsA as models. To water-solublize PLB, the membrane-exposed positions were changed to polar or charged amino acids, while the putative core was left unaltered. We generated water-soluble phospholamban (WSPLB), and compared its properties to its predecessor PLB. As a probe of the correctness of the fold of the water soluble KcsA, the computationally designed proteins contain an agitoxin-2 binding site from a mammalian homologue of the channel. The resulting proteins express in high yield in E. coli and share the intended functional and structural properties with KcsA, including secondary structure, tetrameric quaternary structure, and tight, specific binding to both agitoxin2 and a small molecule channel blocker.
摘要翻译：膜蛋白和水溶性蛋白质共享相似的核心。这种相似性表明，应该可以通过仅突变其暴露于脂质的残留物来水溶性膜蛋白。本文公开了可用于设计螺旋膜蛋白质的水溶性变体的计算工具和方法，其使用五聚磷酸甘油（PLB）和钾通道KcsA作为模型。为了水解PLB，将膜暴露的位置改为极性或带电荷的氨基酸，而假定的核心保持不变。我们产生了水溶性磷脂蛋白（WSPLB），并将其性能与其前身PLB进行了比较。作为水溶性KcsA的倍数的正确性的探针，计算设计的蛋白质含有来自哺乳动物同源物的通道的搅拌毒素-2结合位点。所得蛋白质在大肠杆菌中以高产率表达，并且与KcsA共享预期的功能和结构性质，包括二级结构，四聚体四级结构，以及紧密的，特异性结合于vibroxin2和小分子通道阻断剂。

IPRDB

热门服务

关于我们

友情链接

联系方式