Enzymes found in living organisms have impressive catalytic power. Thanks to enzymes, the chemical reactions that sustain life occur millions of times faster than they would have been without them. Enzymes speed up reactions by helping to reduce the activation energy needed to start them, but how enzymes achieve this has been the subject of intense debate for more than 70 years.
Professor of Pathology and Immunology at Baylor College of Medicine and the Texas Children’s Microbiome Center, Dr. Tor Savage and his colleagues are changing the way we look at this age-old logic. in his work published in chemical scienceThey investigated the similarities and differences between the two mechanisms currently under debate by characterizing the catalytic reactions at the detailed molecular level.
“At the present time, two major different reaction mechanisms are proposed to explain the enzymatic catalytic power,” Savidge said. “One proposes that enzymes lower the activation energy of the reaction through stabilization of transition states (TS) and the other that they do this by destabilizing the ground state (GS) of enzymes. The current view is that these The mechanisms are mutually exclusive.”
First author Dr. Deliang Chen and colleagues took a theoretical approach, taking into account previous findings from the Savage lab, which showed that the substrate and the enzyme’s non-covalent interactions with water are important in terms of the enzyme’s mechanism. Reactions.
“In the biological environment you have to consider water – that it’s going to interfere with the very complex nuclear interactions that are happening in the active site of the enzyme. We need to consider all of them so you need to understand that you Where’s the need for electrostatic interactions. Going in favor of that enzymatic process,” Saviz said. “When you take that into account, you can understand how these mechanisms are working.”
Their analysis led the team to propose something new, that TS and GS are not so different. They use a similar nuclear mechanism to proceed the enzymatic reaction. The mechanism involves water changing the charge of critical residues within the catalytic site to favor the formation of an energetically favorable state that prompts the enzymatic reaction to occur.
“The important, new point here is not how it is achieved, but when it is achieved,” Savidge said. “We have shown that in stabilization of transition states, the charges that drive the reaction are formed before the substrate enters the active site. Whereas in the destabilization ground state this also occurs but after the substrate enters the active site.”
The researchers also proposed that the general mechanism between TS and GS is universal, and could be applied to many enzymatic reactions.
“Our findings have important implications not only for better understanding the catalytic power of enzymes, but also for practical drug design applications.” to use their findings.”
Yibao Li, Xun Li, Xiaolin Fan at Gannon Normal University, and Zhuan Hong at Wuhan University School of Pharmaceutical Sciences also contributed to this work.
This work is supported by grants from the National Natural Science Foundation of China (21763002), the Natural Science Foundation of Jiangxi Province (20202ACBL203008) and the National Institute of Allergy and Infectious Diseases (U01-AI24290 and P01-AI152999).
material provided by Baylor College of Medicine, Ana Maria Rodriguez, Ph.D. Original written by. Note: Content can be edited for style and length.