6O2P

Complex of ivacaftor with cystic fibrosis transmembrane conductance regulator (CFTR)

6O2P の概要

• エントリーDOI: 10.2210/pdb6o2p/pdb
• EMDBエントリー: 0611
• 分子名称: Cystic fibrosis transmembrane conductance regulator, Unknown Peptide, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: abc transporter, anion channel, cystic fibrosis, membrane protein, ivacaftor, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 178062.62

構造登録者

Liu, F.,Zhang, Z.,Chen, J.,Levit, A.,Shoichet, B. (登録日: 2019-02-24, 公開日: 2019-06-26, 最終更新日: 2024-05-15)

主引用文献

Liu, F.,Zhang, Z.,Levit, A.,Levring, J.,Touhara, K.K.,Shoichet, B.K.,Chen, J.
Structural identification of a hotspot on CFTR for potentiation.
Science, 364:1184-1188, 2019

PubMed Abstract: 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.

PubMed: 31221859
DOI: 10.1126/science.aaw7611

実験手法

ELECTRON MICROSCOPY (3.3 Å)