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.
Elaine Schmidt | EurekAlert!
Turning carbon dioxide into liquid fuel
06.08.2020 | DOE/Argonne National Laboratory
Tellurium makes the difference
06.08.2020 | Friedrich-Schiller-Universität Jena
Scientists at the Fraunhofer Institute for Laser Technology ILT have come up with a striking new addition to contact stamping technologies in the ERDF research project ScanCut. In collaboration with industry partners from North Rhine-Westphalia, the Aachen-based team of researchers developed a hybrid manufacturing process for the laser cutting of thin-walled metal strips. This new process makes it possible to fabricate even the tiniest details of contact parts in an eco-friendly, high-precision and efficient manner.
Plug connectors are tiny and, at first glance, unremarkable – yet modern vehicles would be unable to function without them. Several thousand plug connectors...
An international research team has found a new approach that may be able to reduce bone loss in osteoporosis and maintain bone health.
Osteoporosis is the most common age-related bone disease which affects hundreds of millions of individuals worldwide. It is estimated that one in three women...
Traditional single-cell sequencing methods help to reveal insights about cellular differences and functions - but they do this with static snapshots only...
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
06.08.2020 | Earth Sciences
06.08.2020 | Power and Electrical Engineering
06.08.2020 | Life Sciences