Navigation Links
Scientists unveil structure of molecular target of many drugs
Date:10/29/2007

More than 40 years after beta blockers were first used clinically, scientists can finally get a detailed, three-dimensional look at the drugs molecular targetthe beta2-adrenergic receptor. This receptor hails from a family of proteins called G protein-coupled receptors (GPCRs) that control critical bodily functions, several of our senses, and the action of about half of todays pharmaceuticals. Because this is the first known structure of a human GPCR, the work promises not only to speed the discovery of new and improved drugs, but also to broaden our understanding of human health and disease.

Published online in the October 25 issue of Science Express, the research was supported by two major initiatives of the National Institutes of Healththe NIH Roadmap for Medical Research and the Protein Structure Initiative (PSI), which is led by the National Institute of General Medical Sciences. Additional funding came from a Javits Neuroscience Award from the National Institute of Neurological Disorders and Stroke.

To solve the new structure, the researchers overcame daunting scientific obstacles. Many of these difficulties arise because GPCRs are membrane proteinssome of the trickiest molecules to capture in three-dimensional detail because they resist forming crystals, which are needed for structure determination.

Because of their role in so many medically important processes and the great challenges they present for detailed study, membrane proteins have been one focus of the NIH Roadmap, said NIH Director Elias A. Zerhouni, M.D. The determination of this structure is an exciting example of the rewards from the Roadmap investment.

Scientists across the country have tried for years to obtain detailed images of GPCR proteins. Theyve succeeded only once before, in 2000, when a research group determined the structure of a visual pigment in cow eyes. Part of the job was easier then, because the pigment protein is abundant. One of the major challenges in the new study was getting enough of the beta2-adrenergic receptor protein to work with.

After trying in vain to get the protein in its natural form to crystallize, Brian Kobilka and co-workers at Stanford University turned to protein engineering. To overcome problems with the proteins floppiness, they replaced a flexible loop with a more rigid protein structure. Raymond Stevens and co-workers of The Scripps Research Institute managed to coax the intransigent proteins into tiny crystals by devising techniques and environmental conditions that mimicked the proteins native, membrane-like environment. These genetic engineering and crystallization techniques may be broadly applicable to similar proteins, paving the way for more structures from the hundreds of GPCRs encoded in the human genome.

This is an absolutely remarkable advance, said Jeremy M. Berg, Ph.D., director of NIGMS, which, in addition to spearheading the PSI, plays a leading role in the membrane protein Roadmap initiative. Many laboratories around the world are trying to reveal the secrets of these proteins, and this important structure takes the field to a higher level.


'/>"/>

Contact: Emily Carlson
carlsone@nigms.nih.gov
301-496-7301
NIH/National Institute of General Medical Sciences  
Source:Eurekalert

Related biology news :

1. Wisconsin scientists grow critical nerve cells
2. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
3. UCSB scientists probe sea floor venting to gain understanding of early life on Earth
4. UAB scientists discover the origin of a mysterious physical force
5. Fox Chase Cancer Center scientists identify immune-system mutation
6. Scientists Replicate Hepatitis C Virus in Laboratory
7. Scientists detect probable genetic cause of some Parkinsons disease cases
8. Scientists find missing enzyme for tuberculosis iron scavenging pathway
9. Scientists seek answers on what activates deadly anthrax spores
10. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
11. Scientists collaborate to assess health of global environment
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Scientists unveil structure of molecular target of many drugs
(Date:1/31/2017)... Jan. 31, 2017  Spero Therapeutics, LLC, a ... the treatment of bacterial infections, today announced it ... candidates from Pro Bono Bio Ltd (PBB) to ... multi-drug resistant forms of Gram-negative bacteria.   The assets ... Ltd, a PBB group company. "The ...
(Date:1/24/2017)... Jan. 24, 2017 Biopharm Reports has ... laboratory use of nuclear magnetic resonance spectroscopy (NMR). ... and profiled current practices, developments, trends and end-user ... as growth and opportunities. These areas include growth ... instruments, needs and innovation requirements, hyphenated NMR techniques, ...
(Date:1/19/2017)... , Jan. 19, 2017 ... user experience and security for consumer electronics, and ... payment processing systems and cybersecurity solutions, today announced ... enterprises and financial institutions worldwide to bolster security ... the end-to-end secure user authentication platforms they offer, ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... ... February 24, 2017 , ... ... can be safely completed in an ambulatory surgery center (ASC) with satisfactory clinical ... and previous two-year TDR studies. , Jake Lubinski, president of AxioMed, commented ...
(Date:2/24/2017)... San Diego, Calif. (PRWEB) , ... February 24, 2017 , ... ... African food and wine scene. Making stops in several cities, she gained a ... Her culinary adventure began in Stellenbosch, a town in South Africa’s Western Cape province. ...
(Date:2/24/2017)... , Feb. 24, 2017  Aethlon Medical, Inc. (Nasdaq: ... authored by its Chairman and CEO, Jim Joyce ... Munich Security Conference last Saturday, Bill Gates ... kill more people than nuclear weapons. Mr. Gates expressed ... U.K. intelligence agencies, that scientific terrorists have access to ...
(Date:2/24/2017)... , Feb. 24, 2017  Driven by consumers, ... are now the fastest growing categories, finds the ... Actives in Personal Care: Multi-regional Market Analysis and ... management consulting firm Kline. "Biotechnology actives ... make them more effective for skin and hair ...
Breaking Biology Technology: