Cystic fibrosis is an inherited disease afflicting about 70,000 people around the world. Cystic fibrosis patients carry a defective gene that disables or destroys its protein product, which normally regulates the transport of ions across cell borders.
When that transport is disrupted, the viscosity of the mucus coating certain organs becomes too thick. A characteristic feature of the disease is thick mucus buildup in the air passages, which causes difficulty breathing and recurring infections.
While the FDA approved the drug VX-770 (also known by the trade names Kalydeco and Ivacaftor) to ease breathing in people with cystic fibrosis caused by a particular mutation in the CFTR protein (the acronym is short for cystic fibrosis transmembrane conductance regulator), exactly how VX-770 worked in those patients was unknown.
Scientists have understood for some time that normal CFTR regulation requires modification of the protein and binding of a small, energy-providing molecule – adenosine triphosphate, or ATP. But, in their recent Journal of Biological Chemistry "Paper of the Week," Christine Bear and colleagues report that the drug opens both normal and mutant CFTR channels without ATP. Their results indicate that the compound binds to a different site on CTFR than ATP. Significantly, this finding may be useful in developing therapies for cystic fibrosis caused by various CFTR mutations that, like the G551D mutation that was studied, impair ATP-mediated channel regulation.
Bear's group determined how VX-770 works after developing a new experimental system that may have potential for discovering drugs that target the basic defects caused by CFTR mutations, Bear says. The system is useful for identifying compounds that interact with rare mutations such as G551D as well as the major CFTR mutant F508del, she said.
From the article: "CFTR potentiator VX-770 (Ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner" by Paul D.W. Eckford, Canhui Li, Mohabir Ramjeesingh and Christine E. Bear.
Corresponding author: Christine E. Bear, Programme of Molecular Structure & Function, Research Institute, Hospital for Sick Children, in Toronto, Ontario, Canada; email: firstname.lastname@example.org.
Written by Danielle Gutierrez
Angela Hopp | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences