Phosphorylation without ATP

IP7 offers a nonenzymatic alternative for adding phosphate to proteins

Charles Choi(cqchoi@nasw.org)
Dec 16, 2004

For the first time, scientists have described in this week's Science a way for cells to add phosphate groups to proteins that doesn't involve using adenosine triphosphate (ATP) as a donor.

"Nobody had ever dreamt you could phosphorylate with a donor other than ATP," said senior author Solomon Snyder at Johns Hopkins University in Baltimore, who, along with colleagues, suggested a decade ago that inositol pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) might serve as phosphorylating agents due to their highly energetic pyrophosphate bonds.

"ATP phosphorylation has heretofore been regarded as the primary mode of all cellular signaling in biology," Snyder told The Scientist. "IP7 phosphorylation may be of comparable importance, with similarities but major differences—for instance, it is nonenzymatic. It may represent a new form of intracellular signaling."

In the current study, the group synthesized IP7 and radiolabeled the putative donor pyrophosphate. As a control to ensure any apparent...