Researchers clarify function of glucose transport molecule

July 3, 2008

Researchers at the David Geffen School of Medicine at UCLA have solved the structure of a class of proteins known as sodium glucose co-transporters (SGLTs), which pump glucose into cells. These transport proteins are used in the treatment of chronic diarrhea via oral rehydration therapy, saving the lives of millions of children each year. The solution of the SGLT structure will accelerate development of new drugs designed to treat patients with diabetes and cancer.

Led by Jeff Abramson and Ernest Wright of the UCLA Department of Physiology, the research team produced an "atomic snap shot" of an SGLT protein. Using a specialized technique known as X-ray crystallography, they and their team of post-docs and students generated the first high-resolution, three-dimensional picture of a glucose transport protein. The research is published in today's online edition of the journal Science.

"This was a very challenging study that required innovation at each step of the process," said Abramson. "We literally had to invent new approaches to entice the protein into a crystal and then spent years optimizing these crystals to reach a quality suitable for visualization by X-rays. This would not have been possible without high-throughput protein production and purification capabilities."

A tantalizing observation made during the determination of the glucose transporter structure was the possibility for structural similarities with a previously crystallized neurotransmitter transporter molecule. Exploiting these similarities, along with computer modeling of structural dynamics, the researchers obtained the first atomic-level evidence for the mechanism underlying transport of glucose and neurotransmitters (such as serotonin) into cells. These results provide a fundamental understanding of how membrane proteins function in a dynamic manner.

Pharmaceutical companies already have extensive clinical trials underway to evaluate the use of inhibitors targeting SGLT1 and SGLT2 proteins to control blood glucose levels in diabetic patients by blocking intestinal glucose absorption and increasing glucose excretion into the urine. The UCLA findings will dramatically enhance the ability to rationally design these drugs.

In ongoing work, Wright and Abramson are examining the manner in which inhibitors of the transporter proteins modulate function with the goal of facilitating better drug design for the treatment of diabetes, obesity, and cancer.

Source: University of California - Los Angeles

Explore further: Big brains needed carbs—The importance of dietary carbohydrate in human evolution

Related Stories

Atomic view of bacterial enzymes that help human digestion

July 31, 2015

A group of researchers at the University of Waterloo in Ontario, Canada has reached deep into the human gut, plucked out a couple enzymes produced by bacteria residing there and determined their biological activities and ...

Synthetic biology used to engineer new route to biochemicals

June 25, 2015

Living cells can make a vast range of products for us, but they don't always do it in the most straightforward or efficient way. Shota Atsumi, a chemistry professor at UC Davis, aims to address that through "synthetic biology:" ...

Future biosensors could be woven into clothes

June 23, 2015

Commonly used health tests, such as pregnancy and blood sugar tests, involve putting a drop of fluid on a test strip, which is infused with a substance designed to detect a specific molecule.

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.