Journal
CHEMICAL SCIENCE
Volume 13, Issue 27, Pages 8193-8202Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d2sc01994a
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Funding
- National Natural Science Foundation of China [21763002]
- Natural Science Foundation of Jiangxi Province [20202ACBL203008]
- National Institute of Allergy and Infectious Diseases [U01-AI24290, P01-AI152999]
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The catalytic power of enzymes can be achieved through the stabilization of transition states or the destabilization of ground states. Both approaches reduce the free energy barriers of reactions by enhancing the charge densities of catalytic atoms. This study resolves the debate between transition state stabilization and ground state destabilization and contributes to our understanding of catalysis and the design of artificial enzymes.
The origin of the enormous catalytic power of enzymes has been extensively studied through experimental and computational approaches. Although precise mechanisms are still subject to much debate, enzymes are thought to catalyze reactions by stabilizing transition states (TSs) or destabilizing ground states (GSs). By exploring the catalysis of various types of enzyme-substrate noncovalent interactions, we found that catalysis by TS stabilization and the catalysis by GS destabilization share common features by reducing the free energy barriers (Delta G(double dagger)s) of reactions, but are different in attaining the requirement for Delta G(double dagger) reduction. Irrespective of whether enzymes catalyze reactions by TS stabilization or GS destabilization, they reduce Delta G(double dagger)s by enhancing the charge densities of catalytic atoms that experience a reduction in charge density between GSs and TSs. Notably, in TS stabilization, the charge density of catalytic atoms is enhanced prior to enzyme-substrate binding; whereas in GS destabilization, the charge density of catalytic atoms is enhanced during the enzyme-substrate binding. Results show that TS stabilization and GS destabilization are not contradictory to each other and are consistent in reducing the Delta G(double dagger)s of reactions. The full mechanism of enzyme catalysis includes the mechanism of reducing Delta G(double dagger) and the mechanism of enhancing atomic charge densities. Our findings may help resolve the debate between TS stabilization and GS destabilization and assist our understanding of catalysis and the design of artificial enzymes.
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