title: 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.
authors.affiliation: †Departments of Organic Chemistry and ‡Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ronny
authors.initials: R
authors.lastname: Peri-Naor
authors.affiliation: †Departments of Organic Chemistry and ‡Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Ilani
authors.affiliation: †Departments of Organic Chemistry and ‡Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Leila
authors.initials: L
authors.lastname: Motiei
authors.affiliation: †Departments of Organic Chemistry and ‡Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Margulies
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D009841:Oligonucleotides; D010982:Platelet-Derived Growth Factor; D005982:Glutathione Transferase