Effect of Cadmium Ion on alpha-Glucosidase: An Inhibition Kinetics and Molecular Dynamics Simulation Integration Study
| Autor: | Zhi-Rong Lü, Jinhyuk Lee, Yong-Doo Park, Tao Luo, Zhuo-Ming Ye, Li-Mei Yue, Hang Mu |
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| Rok vydání: | 2016 |
| Předmět: |
0106 biological sciences
0301 basic medicine Protein Denaturation Stereochemistry Protein Conformation Kinetics Bioengineering Saccharomyces cerevisiae Molecular Dynamics Simulation 01 natural sciences Biochemistry Analytical Chemistry 03 medical and health sciences Molecular dynamics Protein structure 010608 biotechnology Denaturation (biochemistry) Glycoside Hydrolase Inhibitors Protein secondary structure chemistry.chemical_classification biology Chemistry Organic Chemistry Active site alpha-Glucosidases 030104 developmental biology Enzyme Docking (molecular) biology.protein Environmental Pollutants Cadmium |
| Zdroj: | The protein journal. 35(3) |
| ISSN: | 1875-8355 |
| Popis: | α-Glucosidase is a critical metabolic enzyme that produces glucose molecules by catalyzing carbohydrates. The aim of this study is to elucidate biological toxicity of Cd2+ based on α-glucosidase activity and conformational changes. We studied Cd2+-mediated inactivation as well as conformational modulation of α-glucosidase by using kinetics coupled with simulation of molecular dynamics. The enzyme was significantly inactivated by Cd2+ in a reversibly binding behavior, and Cd2+ binding induced a non-competitive type of inhibition reaction (the K i was calculated as 0.3863 ± 0.033 mM). Cd2+ also modulated regional denaturation of the active site pocket as well as overall partial tertiary structural change. In computational simulations using molecular dynamics, simulated introduction of Cd2+ induced in a depletion of secondary structure by docking Cd2+ near the saccharides degradation at the active site, suggesting that Cd2+ modulating enzyme denaturation. The present study elucidated that the binding of Cd2+ triggers conformational changes of α-glucosidase as well as inactivates catalytic function, and thus suggests an explanation of the deleterious effects of Cd2+ on α-glucosidase. |
| Databáze: | OpenAIRE |
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