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.
Source: Karolinska Institutet
Related stories:
Nobel Prize winner Dr. George Palade dies at 95
(AP) -- Dr. George Palade, who won a Nobel Prize in 1974 for his work isolating and identifying cell structure and helped create one of the leading cell biology programs in the nation at the University of California, San Diego, has died. He was 95.
Scientists discover crucial control in long-lasting immunity
National Institutes of Health (NIH) scientists have identified a protein that plays matchmaker between two key types of white blood cells, T and B cells, enabling them to interact in a way that is crucial to establishing long-lasting immunity after an infection. Their finding may also explain why some individuals who have a genetic defect that prevents them from making this protein—called SAP—suffer from lethal infections with a common virus that otherwise is rarely fatal (Epstein-Barr virus), while others with this genetic defect have problems with B-cell lymphomas.
At 2.8 km down, a 1-of-a-kind microorganism lives all alone
The first ecosystem ever found having only a single biological species has been discovered 2.8 kilometers (1.74 miles) beneath the surface of the earth in the Mponeng gold mine near Johannesburg, South Africa. There the rod-shaped bacterium
Desulforudis audaxviator exists in complete isolation, total darkness, a lack of oxygen, and 60-degree-Celsius heat (140 degrees Fahrenheit).
Research team solves structure of 'beneficial' virus
The 3-D structure of the virus, known as Seneca Valley Virus-001, reveals that it is unlike any other known member of the Picornaviridae viral family, and confirms its recent designation as a separate genus "Senecavirus." The new study reveals that the virus's outer protein shell looks like a craggy golf ball -- one with uneven divets and raised spikes—and the RNA strand beneath it is arranged in a round mesh rather like a whiffleball.
Protection for stressed-out bacteria identified
An international team of researchers is a step closer to understanding the spread of deadly diseases such as listeriosis, after observing for the first time how bacteria respond to stress.
New research may help to design better gene therapy vectors
(PhysOrg.com) -- Research published by scientists from the University of Reading may offer an insight into ways of making safer and more specific gene therapy vectors. The research, published in the journal
Nature Structural and Molecular Biology, describes the structure of the viral fusion protein gp64, which is involved in the mechanism which viruses use to invade host cells. In the past, Bacloviruses have been suggested as possible gene therapy vectors due to the way in which they enter host cells, but there has been little evidence which explain these properties up to now.
Egg whites solve the 3-D problem
The real world is three-dimensional. That's true even in the laboratory, where scientists have to grow cells to study how they develop and what happens when their growth is abnormal.
Atomic-resolution views suggest function of enzyme that regulates light-detecting signals in eye
An atomic-resolution view of an enzyme found only in the eye has given researchers at the University of Washington (UW) clues about how this enzyme, essential to vision, is activated. The enzyme, phosphodiesterase 6 (PDE6), is central to the way light entering the retina is converted into a cascade of signals to the brain.