New discoveries about the power of enzymes could reconstruct biochemistry

Researchers at Stanford University have used over 1,000 x-ray snapshots of the shape of active enzymes to illuminate one of the great mysteries of life. Their findings can impact fields ranging from basic science to inventive science, allowing them to rethink how science is taught in the classroom.

“When I say enzymes speed up a reaction, I mean I’m going to make it as fast as a trillion times faster in some reactions,” said Dan Herschlag, a senior author of the study, in the medical school’s biochemistry. He said he was a professor. “Enzymes are truly amazing little machines, but there’s a lack of understanding exactly how they work.”

According to Herschlag, there are many meaningful ideas and theories, but biochemists are unable to translate those ideas into a specific understanding of chemical and physical interactions that cause the enormous reaction rate of enzymes. It was. As a result, biochemists have no basic understanding and are unable to predict enzyme rates or design new enzymes and nature.

“Using these detailed ensembles of enzyme states, we were able to quantify and explain in detail in chemical detail what the enzyme features provide and how much catalysts provide. ” said Siyuan Du, a doctoral student at Herschlag’s lab. Their research is published in the February 14th issue of the journal Science.

“Our new approaches and understandings begin the path to enabling us to design enzymes that rival those found in nature, but this is just the beginning and far more to achieve that goal. It requires a lot of work,” Herschlag added.

Elusive Entities

Until 1926, biochemists were confused by the exclusive response to living systems and praised them for their mysterious “important forces.” That year, James Sumner sequestered the first known enzyme, urease, in a Nobel Prize-winning study. Since then, biochemists have spent the last century trying to understand how enzymes make reactions very quickly and concrete. In other words, they explained how they function in words rather than quantitatively, which led to views that contrasted with discussions about how they function.

Du and Herchlag were built on the widely held view among biophysicists that enzymes are not a single structure. Instead, they focus on what is called “ensembles,” showing how enzymes migrate catalytically between different physical states (or conformational ensembles).

“All existing models use some degree of positioning of the group of chemicals and chemicals that react on enzymes that support the reaction,” Herschlag explained. However, with this new “ensemble” approach, there is no way to measure it without this new “ensemble” approach taken by Hirschlug and Du, and debate is escalating about how important positioning is.

“The enzymes are constantly moving in an ensemble of states, and the rate of reaction is determined by the probability within the ensemble,” Du explained in detail.

As their subject, the authors chose a family of enzymes known as serine proteases. This is the family that most biochemistry textbooks use to explain the enzyme process to budding biochemists.

These ensembles were explored and the reaction state of the enzyme was compared with the state of the non-catalytic enzyme in pure water. Hirschlag and Du degraded individual energy contributions and enzyme catalysts at the exact location where enzymes and target molecules meet during the reaction known as the active site. Understand how they function chemically and physically to accelerate the response.

Potential energy

In one example, DU pointed out that the oxygen atom of the enzyme at the active site “attacks” the carbon atom of the molecule. It’s like a coiled spring, Du said, but the way in which individual atoms and atom moves move is focused on the smooth movement of the spring and the different ways, making it a very literary interpretation. I warned against it.

“There’s a bit of tension that forces these atoms together. When a reaction occurs, all that pent-up energy advances the reaction, leading to a much faster response,” she said.

Du then noted that, as expected, these catalytic strategies appeared not only across all serine proteases, but also over 100 other enzymes.

“Nature has independently evolved these mechanisms in multiple enzyme families. This is not an isolated feature, but a catalytic mechanism that has been discovered many times throughout evolution. And it is a new enzyme, and “We’ll do that,” Du said.

Regarding what comes next, Herschlag and Du are the ability to describe the extraordinary abilities of these important biochemicals in simple chemical terms, revolutionizing how biochemistry is taught, and many He said it could speed up new science in key areas.

“Conclusion,” said Hirschrag, “We need to understand enzymes better and better before we can engineer anything better.”