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Finding of long-sought drug target structure may expedite drug discovery
Date:3/15/2011

body at its smallest components, we can learn how to improve whole-body health."

A receptor is a protein that receives and sends signals to other molecules. The three-dimensional structure of the solved receptor also contains an agonist a chemical command signal from outside the cell in this case, an adenosine molecule. Similar to the function of a telephone receiver, the receptor acts as a sensor, picking up the message from the agonist and transmitting its information, which begins processes inside the cell.

The researchers discovered that a previously known agonist molecule would bind to its receptor target in a way that stabilizes the protein for crystallization. Once crystallized, the structure can be seen by bombarding it with X-rays. The agonist solidifies the protein by connecting to multiple parts of the receptor with its molecular arms, in the process initiating the function of the entire structure. This adenosine receptor, called A2A, counteracts inflammation and responds to organs in distress. It belongs to the G-protein coupled receptor family, which is involved in processes necessary for many drugs currently in use to take effect. These findings may lead to new drugs for many diseases.

The research was also supported by the National Cancer Institute and the National Institute of General Medical Sciences, both components of the NIH.

"Long-term NIH technology investments in structural biology, including the Protein Structure Initiative, have brought diverse teams of investigators together and yielded powerful methods like the ones used in this study," said NIGMS Director Dr. Jeremy M. Berg. "Receptors must undergo substantial changes in shape in order to function, and revealing these molecular dances in such great detail is an impressive accomplishment."


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Contact: Amy Reiter
NIDDKMedia@mail.nih.gov
301-496-3583
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
Source:Eurekalert  

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