WASHINGTON: Scientists have managed to reveal the crystal structure of a human membrane protein, LTC4 synthase, which has a major influence on the development of Asthma.
LTC4 synthase is tremendously difficult to analyse, and previously only low-resolution information had been available on two membrane protein structures from humans.
Now, researchers at Karolinska Institute in Sweden believe that their work will facilitate the development of new and better therapeutics against inflammations in the pulmonary tract.
Asthma attacks are caused by a severe inflammatory reaction in the airways, a reaction that is largely due to actions of LTC4 synthase. For this reason Asthma medicines often aim at blocking the downstream effects of LTC4 synthase. However, there is a need for new pharmaceutical alternatives, as not all patients respond to the existing medicines.
Now, scientists at the Department of Medical Biochemistry and Biophysics have, with the help of the two EU networks “Eicosanox” and “E-Mep”, elucidated the three dimensional structure of the LTC4 synthase at 2.0 Å resolution.
It is clear from the structure that the protein has three identical subunits, each of them consisting of four spiral structures that cover the nuclear membrane. Also the exact position and characteristics of the active sites, where activating or blocking molecules can attach, have been identified. With this knowledge it is now achievable to shape new molecules that can block the LTC4 synthase.
The new results are also very important as they can lead the way for the development of new and more effective therapeutics against other diseases. Some 40 percent of the proteins of interest for pharmaceutical developments are membrane proteins. The current study is likely to lead the way for the determination of structures of other human membrane proteins.
LTC4 synthase is tremendously difficult to analyse, and previously only low-resolution information had been available on two membrane protein structures from humans.
Now, researchers at Karolinska Institute in Sweden believe that their work will facilitate the development of new and better therapeutics against inflammations in the pulmonary tract.
Asthma attacks are caused by a severe inflammatory reaction in the airways, a reaction that is largely due to actions of LTC4 synthase. For this reason Asthma medicines often aim at blocking the downstream effects of LTC4 synthase. However, there is a need for new pharmaceutical alternatives, as not all patients respond to the existing medicines.
Now, scientists at the Department of Medical Biochemistry and Biophysics have, with the help of the two EU networks “Eicosanox” and “E-Mep”, elucidated the three dimensional structure of the LTC4 synthase at 2.0 Å resolution.
It is clear from the structure that the protein has three identical subunits, each of them consisting of four spiral structures that cover the nuclear membrane. Also the exact position and characteristics of the active sites, where activating or blocking molecules can attach, have been identified. With this knowledge it is now achievable to shape new molecules that can block the LTC4 synthase.
The new results are also very important as they can lead the way for the development of new and more effective therapeutics against other diseases. Some 40 percent of the proteins of interest for pharmaceutical developments are membrane proteins. The current study is likely to lead the way for the determination of structures of other human membrane proteins.
2 Comments