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Speeding up drug discovery with rapid 3-D mapping of proteins
Date:5/30/2012

LA JOLLA, CA----A new method for rapidly solving the three-dimensional structures of a special group of proteins, known as integral membrane proteins, may speed drug discovery by providing scientists with precise targets for new therapies, according to a paper published May 20 in Nature Methods.

The technique, developed by scientists at the Salk Institute for Biological Studies, provides a shortcut for determining the structure of human integral membrane proteins (hIMPs), molecules found on the surface of cells that serve as the targets for about half of all current drugs.

Knowing the exact three-dimensional shape of hIMPs allows drug developers to understand the precise biochemical mechanisms by which current drugs work and to develop new drugs that target the proteins.

"Our cells contain around 8,000 of these proteins, but structural biologists have known the three-dimensional structure of only 30 hIMPs reported by the entire field over many years," says Senyon Choe, a professor in Salk's Structural Biology Laboratory and lead author on the paper. "We solved six more in a matter of months using this new technique. The very limited information on the shape of human membrane proteins hampers structure-driven drug design, but our method should help address this by dramatically increasing the library of known hIMP structures."

Integral membrane proteins are attached to the membrane surrounding each cell, serving as gateways for absorbing nutrients, hormones and drugs, removing waste products, and allowing cells to communicate with their environment. Many diseases, including Alzheimer's, heart disease and cancer have been linked to malfunctioning hIMPs, and many drugs, ranging from aspirin to schizophrenia medications, target these proteins.

Most of the existing drugs were discovered through brute force methods that required screening thousands of potential molecules in laboratory studies to determine if t
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Contact: Andy Hoang
ahoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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