Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Crystal structure enables tailoring of pharmaceuticals against asthma

17.07.2007
Researchers at Karolinska Institutet in Sweden have managed to elucidate the crystal structure of a human membrane protein – LTC4 synthase – which has a major influence on the development of asthma. LTC4 synthase is extremely difficult to analyze, and previously only low resolution information has been available on two membrane protein structures from human. The scientists now believe that their work will enable the development of new and better therapeutics against inflammations in the pulmonary tract.

Asthma attacks are caused by an acute 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, since not all patients respond to the existing medicines.

Scientists at the Department of Medical Biochemistry and Biophysics have now, 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 (1 Å = 1 Ångström = 10-10 m = 0,000 000 000 1 m). It is clear from the structure that the protein has three identical subunits, each of them consisting of four spiral structures that span the nuclear membrane. Also the exact position and characteristics of the active sites, where activating or blocking molecules can bind, have been identified. With this knowledge it is now possible to tailor 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 % of the proteins of interest for pharmaceutical developments are membrane proteins. Until now detailed structural information on these proteins has been absent, and therefore it has been difficult to fully understand their function. The present study is likely to lead the way for the determination of structures of other human membrane proteins. The elucidation of more membrane protein structures will help us understand fundamental processes that take place in the cell membranes.

Facts: Proteins consist of a chain of amino acids. The length of this chain can range from a few to thousands of amino acids. The chain is then folded in a characteristic way and the 3-D structure can bind different molecules. Determining a protein structure and its biochemical characteristics helps us understand its function, and to design blocking or activating molecules which can serve as medicines. A known protein structure therefore makes it easier and faster to develop new pharmaceuticals.

The EU network EICOSANOX brings together leading scientists from Europe and Canada, and is coordinated by Karolinska Institutet.

Publication:

“Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase”
Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggström JZ, Nordlund P.

Nature, AOP 15 July 2007

Katarina Sternudd | alfa
Further information:
http://www.ki.se

Further reports about: Asthma LTC4 Pharmaceutical amino acid protein structure synthase

More articles from Life Sciences:

nachricht Cells communicate in a dynamic code
19.02.2018 | California Institute of Technology

nachricht Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Japanese researchers develop ultrathin, highly elastic skin display

19.02.2018 | Information Technology

Dispersal of Fish Eggs by Water Birds – Just a Myth?

19.02.2018 | Ecology, The Environment and Conservation

Studying mitosis' structure to understand the inside of cancer cells

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>