CRYSTAL STRUCTURE DETERMINATION OF M2 PROTON CHANNEL

M2 质子通道的晶体结构测定

• 批准号: 7957290
• 负责人: Runa Acharya
• 金额: $ 2.01万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957290
• 关键词: Amantadine; Amino Acids; Ants; Birds; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Drug resistance; Family suidae; Funding; Grant; Human; Influenza; Influenza A virus; Institution; Light; M2 protein; Pharmaceutical Preparations; Proteins; Protons; Research; Research Personnel; Resolution; Resources; Rimantadine; Source; Structure; Synchrotrons; Transmembrane Domain; United States National Institutes of Health; Viral; Work; alpha helix; design; mutant

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.

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