Zimanyi, Chen, and Kang: One enzyme maintains a cell’s pool of DNA building blocks


February 2, 2016

Cell survival depends on having a plentiful and balanced pool of the four chemical building blocks that make up DNA — the deoxyribonucleosides deoxyadenosine, deoxyguanosine, deoxycytidine, and thymidine, often abbreviated as A, G, C, and T. However, if too many of these components pile up, or if their usual ratio is disrupted, that can be deadly for the cell. A new study from MIT chemists sheds light on a longstanding puzzle: how a single enzyme known as ribonucleotide reductase (RNR) generates all four of these building blocks and maintains the correct balance among them. The paper’s lead author is former MIT graduate student Christina Zimanyi. Other authors are graduate students Percival Yang-Ting Chen and Gyunghoon Kang, and former graduate student Michael Funk.

Unlike RNR, most enzymes specialize in converting just one type of molecule to another, says Catherine Drennan, a professor of chemistry and biology at MIT. “Ribonucleotide reductase is very unusual. I’ve been fascinated with this question of how it actually works and how this enzyme’s active site can be molded into four different shapes.” Drennan and colleagues report in the journal eLife that RNR’s interactions with its downstream products via a special effector site causes the enzyme to change its shape, determining which of the four DNA building blocks it will generate. While many other enzymes are controlled by effectors, this type of regulation usually turns enzyme activity up or down. “I can’t think of any other examples of effector binding changing what the substrate is. This is just very unusual,” Drennan says. Read more

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