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

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