How do you capture a cellular process that transpires in the blink of an eye? Biochemists at MIT have devised a way to trap and visualize a vital enzyme at the moment it becomes active — informing drug development and revealing how biological systems store and transfer energy.
The enzyme, ribonucleotide reductase (RNR), is responsible for converting RNA building blocks into DNA building blocks, in order to build new DNA strands and repair old ones. RNR is a target for anti-cancer therapies, as well as drugs that treat viral diseases like HIV/AIDS. But for decades, scientists struggled to determine how the enzyme is activated because it happens so quickly. Now, for the first time, researchers have trapped the enzyme in its active state and observed how the enzyme changes shape, bringing its two subunits closer together and transferring the energy needed to produce the building blocks for DNA assembly.
Before this study, many believed RNR’s two subunits came together and fit with perfect symmetry, like a key into a lock. “For 30 years, that’s what we thought,” says Catherine Drennan, an MIT professor of chemistry and biology and a Howard Hughes Medical Institute investigator. “But now, we can see the movement is much more elegant. The enzyme is actually performing a ‘molecular square dance,’ where different parts of the protein hook onto and swing around other parts. It’s really quite beautiful.”
