Protein–Protein Communication and Enzyme Activation Mediated by a Synthetic Chemical Transducer

Abstract

The design and function of a synthetic "chemical transducer" that can generate an unnatural communication channel between two proteins is described. Specifically, we show how this transducer enables platelet-derived growth factor to trigger (in vitro) the catalytic activity of glutathione-s-transferase (GST), which is not its natural enzyme partner. GST activity can be further controlled by adding specific oligonucleotides that switch the enzymatic reaction on and off. We also demonstrate that a molecular machine, which can regulate the function of an enzyme, could be used to change the way a prodrug is activated in a "programmable" manner.