6O2P
Complex of ivacaftor with cystic fibrosis transmembrane conductance regulator (CFTR)
Summary for 6O2P
| Entry DOI | 10.2210/pdb6o2p/pdb |
| EMDB information | 0611 |
| Descriptor | Cystic fibrosis transmembrane conductance regulator, Unknown Peptide, MAGNESIUM ION, ... (7 entities in total) |
| Functional Keywords | abc transporter, anion channel, cystic fibrosis, membrane protein, ivacaftor, hydrolase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 178062.62 |
| Authors | Liu, F.,Zhang, Z.,Chen, J.,Levit, A.,Shoichet, B. (deposition date: 2019-02-24, release date: 2019-06-26, Last modification date: 2024-05-15) |
| Primary citation | 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 Cited by 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: 31221859DOI: 10.1126/science.aaw7611 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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