CRYSTAL STRUCTURE DETERMINATION OF M2 PROTON CHANNEL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 来自甲型流感病毒的M2蛋白形成病毒包膜的重要组分。 它是一种pH激活的质子通道，对病毒复制至关重要。 M2是具有单个跨膜（TM）α-螺旋的97个氨基酸的蛋白质，其组装以形成同源四聚体通道，并且是抗流感药物金刚烷胺和金刚乙胺的靶标。这些药物被广泛使用了三十多年，然而，在过去的几年里，人类、鸟类和猪对这些药物的耐药性已经达到90%以上。为了理解质子传导机制和设计有效的突变体新药，最近，我们已经解决了蛋白质TM区域的晶体结构（在3.5分辨率下）和不存在通道阻断药物（在2.0分辨率下）。 在我们的持续努力中，我们正在努力获得不同构建体的野生型蛋白质的高分辨率结构，有和没有药物存在，以及耐药性突变体。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The M2 protein from influenza A virus forms an essential component of viral envelope. It is a pH-activated proton channel and is crucial for viral replication. The M2 is a 97 amino acid protein with a single transmembrane (TM) alpha-helix, that assembles to form a homotetrameric channel and is the target of the ant-influenza drugs amantadine and rimantadine. These drugs were used prophylactically for over three decades, however, in the last few years resistance to these drugs in humans, birds, and pigs has reached over 90%. With an envision to understand the proton conduction mechanism and designing effective new drug for mutants, recently, we have solved the crystal structure of the TM region of protein ( at 3.5 resolution ) with and without presence of channel blocking drug (at 2.0 resolution). In our continuing effort, we are working towards obtaining high resolution structures of wild type protein of different constructs, with and without presence of drug, and drug resistance mutant.