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Improved molecular switch could serve as sensor, medical tool

Improving significantly on an early prototype, Johns Hopkins University researchers have found a new way to join two unrelated proteins to create a molecular switch, a nanoscale "device" in which one biochemical partner controls the activity of the other. Lab experiments have demonstrated that the new switch performs 10 times more effectively than the early model and that its "on-off" effect is repeatable.

The new technique to produce the molecular switch and related experimental results are reported in the November issue of the journal Chemistry & Biology. The paper builds on earlier research, led by Marc Ostermeier, which demonstrated that it was possible to create a fused protein in which one component sends instructions to the other. The second then carries out the task.

"Last year, we reported that we'd used protein engineering techniques to make a molecular switch, putting together two proteins that normally had nothing to do with one another, but the switching properties of that version were insufficient for many applications," said Ostermeier, an assistant professor in the Department of Chemical and Biomolecular Engineering at Johns Hopkins. "With the new technique, we've produced a molecular switch that's over 10 times more effective. When we introduce this switch into bacteria, it transforms them into a working sensor."

As in their earlier experiments, Ostermeier's team made a molecular switch by joining two proteins that typically do not interact: beta-lactamase and the maltose binding protein found in a harmless form of E. coli bacteria. Each of these proteins has a distinct activity that makes it easy to monitor. Beta-lactamase is an enzyme that can disable and degrade penicillin-like antibiotics. Maltose binding protein binds to a type of sugar called maltose that E. coli cells can use as food.

In the previous experiments, the researchers used a cut-and-paste process to insert the beta-lactamase protein into a v
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Contact: Phil Sneiderman
prs@jhu.edu
443-287-9960
Johns Hopkins University
29-Nov-2004


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