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Effect of Cadmium Ion on alpha-Glucosidase: An Inhibition Kinetics and Molecular Dynamics Simulation Integration Study

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Abstract

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.

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Abbreviations

pNPG:

p-Nitrophenyl α-d-glucopyranoside

pNP:

4-Nitrophenol

ANS:

1-Anilino-8-naphthalenesulfonate

MD:

Molecular dynamics

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Acknowledgments

Dr. Hang Mu was supported by a grant from the Science and Technology Planning Project of Jiaxing (No. 2013AY21032). Dr. Jinhyuk Lee was supported through grants from the KOBIC Research Support Program, KRIBB Research Initiative Program, and the Pioneer Research Center Program through the National Research Foundation of Korea funded through the Ministry of Science, ICT & Future Planning (2013M3C1A3064780). Dr. Yong-Doo Park was supported through a grant from the Zhejiang Provincial Natural Science Foundation of China, “Towards studying the function of C3dg protein and elucidating its role in the pathogenesis of atopic dermatitis” (Grant No. LY14H110001) and a fund from the Science and Technology Planning Project of Jiaxing (No. 2014AY21026).

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    Authors and Affiliations

    1. Department of Epidemiology, School of Public Health and Tropical Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou, 510515, People’s Republic of China

      Tao Luo, Li-Mei Yue & Zhuo-Ming Ye

    2. Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea

      Jinhyuk Lee

    3. Department of Nanobiotechnology and Bioinformatics, University of Sciences and Technology, Daejeon, 305-350, Korea

      Jinhyuk Lee

    4. Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing, 314006, People’s Republic of China

      Zhi-Rong Lü, Hang Mu & Yong-Doo Park

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    1. Tao Luo
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    2. Jinhyuk Lee
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    3. Zhi-Rong Lü
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    4. Hang Mu
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    7. Zhuo-Ming Ye
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    Correspondence to Zhuo-Ming Ye.

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    Tao Luo and Jinhyuk Lee authors have equally contributed to this study.

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    Luo, T., Lee, J., Lü, ZR. et al. Effect of Cadmium Ion on alpha-Glucosidase: An Inhibition Kinetics and Molecular Dynamics Simulation Integration Study. Protein J 35, 218–224 (2016). https://doi.org/10.1007/s10930-016-9664-z

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