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First structure of transporter enzyme family is solved

Scientists are a step closer to understanding how essential nutrients, vitamins and minerals are ferried into cells.

For the first time, a member of the Major Facilitator Superfamily (MFS) of transport proteins, found in almost every form of life, has been visualised by researchers from Imperial College London and the University of California, Los Angeles.

Reporting in Science today, the researchers reveal the structure of lactose permease, the enzyme in Esherichia coli that helps pump lactose, the major sugar in milk, into cells. Using the structure data, the researchers propose a possible mechanism of action, which is likely to be common among other transport proteins in this family.

Professor So Iwata of Imperial's Centre for Structural Biology and senior author of the paper explains: "Membrane transport proteins play major roles in depression, stroke and diabetes. Unravelling their structure is critical not only for understanding how we function, but also to improve drug design. Indeed, two of the most widely prescribed drugs in the world, Prozac and Prilosec, act through these proteins.

"The three-dimensional structure of lactose permease gives us our first real picture of how the family of enzymes work. For example, in humans the MFS transporter GLUT4 is responsible for increased glucose uptake in response to insulin stimulation, which has important implications for diabetes. Using the structure of lactose permease we can model GLUT4 and design drugs to control glucose uptake."

Membrane transport proteins play a crucial role in maintaining the selective internal environment of cells. They act as gatekeepers by controlling the entry of nutrients and the exit of waste products. But only four transport protein structures are presently known, compared with over 30,000 soluble protein structures, because they are notoriously difficult to crystallise.

Professor Iwata's Laboratory of Membrane Protein Crystallograph
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Contact: Judith H Moore
j.h.moore@imperial.ac.uk
020-7594-6702
Imperial College London
31-Jul-2003


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