Asset Details
Do you wish to reserve the book?
Structural identification of a hotspot on CFTR for potentiation
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Structural identification of a hotspot on CFTR for potentiation
Do you wish to request the book?
Structural identification of a hotspot on CFTR for potentiation
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Structural identification of a hotspot on CFTR for potentiation
2019
Overview
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 ofCFTR. 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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Chloride Channel Agonists - chemistry
/ Chloride Channel Agonists - pharmacology
/ Chloride Channel Agonists - therapeutic use
/ Cystic Fibrosis - drug therapy
/ Cystic Fibrosis Transmembrane Conductance Regulator - chemistry
/ Cystic Fibrosis Transmembrane Conductance Regulator - genetics
/ Drugs
/ Drugs, Investigational - chemistry
/ Drugs, Investigational - pharmacology
/ Drugs, Investigational - therapeutic use
/ Humans
/ Ion flux
/ Mutation
