Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aaw7611 |
Structural identification of a hotspot on CFTR for potentiation | |
Liu, Fangyu1,2; Zhang, Zhe1; Levit, Anat3; Levring, Jesper1; Touhara, Kouki K.4,6; Shoichet, Brian K.3; Chen, Jue1,5 | |
2019-06-21 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6446页码:1184-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function of CFTR. Here, we report two cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administration (FDA)-approved drug ivacaftor at 3.3-angstrom resolution and the other with an investigational drug, GLPG1837, at 3.2-angstrom resolution. These two drugs, although chemically dissimilar, bind to the same site within the transmembrane region. Mutagenesis suggests that in both cases, hydrogen bonds provided by the protein are important for drug recognition. The molecular details of how ivacaftor and GLPG1837 interact with CFTR may facilitate structure-based optimization of therapeutic compounds. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000472175100042 |
WOS关键词 | CYSTIC-FIBROSIS ; STRUCTURE VALIDATION ; ATOM CONTACTS ; IN-VITRO ; PHOSPHORYLATION ; IVACAFTOR ; VX-770 ; MODEL ; REFINEMENT ; MOLPROBITY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201699 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Rockefeller Univ, Lab Membrane Biophys & Biol, New York, NY 10065 USA; 2.Rockefeller Univ, Triinst Training Program Chem Biol, New York, NY 10065 USA; 3.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA; 4.Rockefeller Univ, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA; 5.Howard Hughes Med Inst, Chevy Chase, MD 20815 USA; 6.Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA |
推荐引用方式 GB/T 7714 | Liu, Fangyu,Zhang, Zhe,Levit, Anat,et al. Structural identification of a hotspot on CFTR for potentiation[J]. SCIENCE,2019,364(6446):1184-+. |
APA | Liu, Fangyu.,Zhang, Zhe.,Levit, Anat.,Levring, Jesper.,Touhara, Kouki K..,...&Chen, Jue.(2019).Structural identification of a hotspot on CFTR for potentiation.SCIENCE,364(6446),1184-+. |
MLA | Liu, Fangyu,et al."Structural identification of a hotspot on CFTR for potentiation".SCIENCE 364.6446(2019):1184-+. |
条目包含的文件 | 条目无相关文件。 |
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