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Changing the perspective on the origin of enzymatic catalytic power

Changing the perspective on the origin of enzymatic catalytic force

Graphical representation of the steps in an enzymatic reaction. Credit: Wikimedia Commons

The enzymes found in living organisms have impressive catalytic power. Thanks to enzymes, the chemical reactions that sustain life happen millions of times faster than without enzymes. Enzymes speed up reactions by helping to lower the activation energy needed to start them, but for over 70 years the way enzymes accomplish this has been the subject of intense debate.

dr. Tor Savidge, a professor of pathology and immunology at Baylor College of Medicine and the Texas Children’s Microbiome Center, and his colleagues are changing the way this old argument is viewed. In their work published in Chemical Sciencesthey examined the similarities and differences between the two mechanisms currently under discussion by characterizing catalytic reactions at a detailed molecular level.

“Two major different reaction mechanisms are currently proposed to explain enzymatic catalytic force,” Savidge said. “One proposes that enzymes lower the activation energy of the reaction via transition state (TS) stabilization and the other that they do this by destabilizing the ground state (GS) of enzymes. The current idea is that these mechanisms are mutually exclusive.”

First author Dr. Deliang Chen of Gannan Normal University in China and his colleagues took a theoretical approach, taking into account previous findings from the Savidge lab showing that the non-covalent interactions of substrates and enzymes with water are important in terms of the mechanism of the enzymatic reactions.

“In a biological environment, you have to consider the water — that it’s going to interfere with the very complex atomic interactions that take place in the active site of the enzyme. We have to consider all of them to understand where exactly you have to have electrostatic interactions that are will promote that enzymatic process,” Savidge said. “If you take that into account, you can understand how these mechanisms work.”

Their analyzes led the team to propose something new: that TS and GS are not so different after all. They use a similar atomic mechanism to drive the enzymatic reaction forward. The mechanism involves water changing the charge of important residues in the catalytic site in a way that promotes the formation of an energetically favorable state that stimulates the enzymatic reaction.

“The important, new point here is not how this is achieved, but when it is achieved,” Savidge said. “We have shown that in transition state stabilization, the charges that propel the reaction are formed before the substrate enters the active site. While in the destabilization ground state this also occurs, but after the substrate enters the active site.”

The researchers also suggested that the common mechanism between TS and GS is universal; it can be applied to many enzymatic reactions.

Their findings have important implications not only for helping researchers better understand the catalytic power of enzymes, but also for practical applications for drug design.

“We are using our findings to explore microbial enzymatic catalysis in different environments more deeply and to design artificial enzymes,” Savidge said.

Yibao Li, Xun Li, Xiaolin Fan, at Gannan Normal University, and Xuechuan Hong at Wuhan University School of Pharmaceutical Sciences also contributed to this work.


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More information:
Deliang Chen et al, Key difference between transition state stabilization and ground state destabilization: increasing atomic charge densities before or during enzyme-substrate binding, Chemical Sciences (2022). DOI: 10.1039/D2SC01994A

Provided by Baylor College of Medicine


Quote: Changing the perspective on the origin of enzymatic catalytic power (2022, July 28) retrieved July 28, 2022 from https://phys.org/news/2022-07-perspective-enzymatic-catalytic-power.html

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