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:6/9/2016)... , June 9, 2016 ... deploy Teleste,s video security solution to ensure the safety of ... during the major tournament Teleste, an ... systems and services, announced today that its video security solution ... to back up public safety across the country. The ...
(Date:6/2/2016)... Perimeter Surveillance & Detection Systems, Biometrics & ... & Other Service  The latest report from ... of the global Border Security market . Visiongain ... billion in 2016. Now: In November 2015 ... and hardware technologies for advanced video surveillance. ...
(Date:5/12/2016)... May 12, 2016 WearablesResearch.com , a ... the overview results from the Q1 wave of its ... wave was consumers, receptivity to a program where they ... a health insurance company. "We were surprised ... says Michael LaColla , CEO of Troubadour Research, ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and ... and the 6000i models are higher end machines that use the more unconventional z-dimension ... light beam from the bottom of the cuvette holder. , FireflySci has developed ...
(Date:6/23/2016)... TORONTO , June 23, 2016 /PRNewswire/ - ... Ontario biotechnology company, Propellon ... the development and commercialization of a portfolio of ... cancers. Epigenetic targets such as WDR5 represent an ... contribute significantly in precision medicine for cancer patients. ...
(Date:6/23/2016)... June, 23, 2016  The Biodesign Challenge (BDC), a ... ways to harness living systems and biotechnology, announced its ... in New York City . ... students, showcased projects at MoMA,s Celeste Bartos Theater during ... , MoMA,s senior curator of architecture and design, and ...
(Date:6/23/2016)... June 23, 2016 Apellis Pharmaceuticals, Inc. ... clinical trials of its complement C3 inhibitor, APL-2. ... multiple ascending dose studies designed to assess the ... subcutaneous injection in healthy adult volunteers. ... as a single dose (ranging from 45 to ...
Breaking Biology Technology: