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Medicine

Scientists Find Key to Unlocking Mysterious Enzyme

Researchers discover a low-barrier hydrogen bond that powers long-range radical transfer in an enzyme crucial for DNA synthesis.

Illustration: Blue Dot News

1 min read

In a hidden corner of our cells, a tiny molecule is orchestrating a complex dance that allows us to pass on our genetic blueprint from one generation to the next. This molecular machinery, known as ribonucleotide reductase, is responsible for converting the raw materials of life - RNA and DNA building blocks - into the essential components of our very existence.

At its heart lies a mysterious connection between two seemingly unrelated partners: a tiny molecule called DOPA• and the protein's own internal hydrogen bonds. This low-barrier hydrogen bond acts like a switch, turning on a radical transfer that spans over 30 Å - an astonishing distance that defies conventional chemical intuition. As our researchers have discovered, this radical is not just a fleeting byproduct but a crucial component in the enzyme's catalytic power.

So why does this discovery matter? Because it reveals a fundamental truth about the intricate web of connections within living molecules. The humble low-barrier hydrogen bond has emerged as a key player in protein chemistry, hinting at the vast and subtle quantum effects that govern our biology. By unraveling this mystery, we gain a deeper appreciation for the intricate machinery that underlies life itself - a machine that is both fragile and resilient, governed by the same laws of physics that shape the universe.

The people behind the work

  • Sirohiwal A et al.

    Author

    Published in Proceedings of the National Academy of Sciences of the United States of America

Source: Proceedings of the National Academy of Sciences of the United States of America

Sources & Verification

Every statement in this story is drawn from the facts below. Each is linked to a primary or reputable source — follow any citation to check it for yourself.

  1. Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotide (RNA) to deoxyribonucleotide (DNA) building blocks initiated by a long-range (>30 Å) proton-coupled electron transfer (PCET) by mechanistic principles that remain much debated. Proceedings of the National Academy of Sciences of the United States of America
  2. We show that DOPA• is redox-tuned by a low-barrier hydrogen bond (LBHB), with a delocalized proton that provides the catalytic power for the ribonucleotide reduction. Proceedings of the National Academy of Sciences of the United States of America
  3. We find that the LBHB couples to an extended hydrogen-bonded network, with distant mutations resulting in the loss of radical formation, and providing key molecular insight into the long-range radical transport mechanism in RNRs. Proceedings of the National Academy of Sciences of the United States of America
  4. On a general level, our findings support the direct involvement of LBHB in protein chemistry and the importance of quantum effects in enzyme catalysis. Proceedings of the National Academy of Sciences of the United States of America

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