The Catalytic Mechanism and Activity Modulation of Manganese Superoxide Dismutase
10.16476/j.pibb.2022.0572
- VernacularTitle:锰超氧化物歧化酶的催化原理与酶活性调节机制
- Author:
Xu ZHANG
1
;
Lei ZHANG
2
;
Peng-Lin XU
3
;
Tian-Ran LI
4
;
Rui-Qing CHAO
5
;
Zheng-Hao HAN
6
Author Information
1. Department of Biochemistry and Molecular Biology, Academy of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
2. School of Physical Education, Zhengzhou University, Zhengzhou 450001, China
3. Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001, China
4. Department of Clinical Medicine, Medical School, Zhengzhou University, Zhengzhou 450001, China
5. School of Chemistry, Zhengzhou University, Zhengzhou 450001, China
6. Henan Vocational College of Applied Technology, Zhengzhou 450042, China
- Publication Type:Journal Article
- Keywords:
manganese superoxide dismutase (MnSOD);
allosteric regulation;
covalent modification;
reactive oxygen species (ROS);
redox;
temperature;
enzyme catalytic mechanisms
- From:
Progress in Biochemistry and Biophysics
2024;51(1):20-32
- CountryChina
- Language:Chinese
-
Abstract:
Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.
