Effect of Ca^<2+> on the activity and structure of α-glucosidase : Inhibition kinetics and molecular dynamics simulations(ENZYMOLOGY, PROTEIN ENGINEERING, AND ENZYME TECHNOLOGY)

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概要

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• Understanding the mechanism of inhibition of α-glucosidase (EC 3.2.1.20) is clinically important because of the involvement of this enzyme in type 2 diabetes mellitus. In this study, we conducted inhibition kinetics of α-glucosidase with Ca^<2+> and 10-ns molecular dynamics simulations. We found that direct binding of Ca^<2+> to the enzyme induced structural changes and inhibited enzyme activity. Ca^<2+> inhibited α-glucosidase in a mixed-type reaction (K_i=27.0 ± 2.0 mM) and directly induced the unfolding of α-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca^<2+> ions may interact with α-glucosidase residues and that the Ca^<2+> binding sites are associated with the structural changes in α-glucosidase. Our study provides insight into the mechanism of the Ca^<2+>-induced structural changes in α-glucosidase and the inhibition of ligand binding. These results suggest that Ca^<2+> could act as a potent inhibitor of α-glucosidase for the treatment of type 2 diabetes mellitus.

• 公益社団法人日本生物工学会の論文

著者

• Zhou Hai-meng

  School Of Life Sciences Tsinghua University

• Zhang Qian

  School Of Earth And Space Sciences Peking Univ.

• Lu Zhi-rong

  Zhejiang Provincial Key Laboratory Of Applied Enzymology Yangtze Delta Region Institute Of Tsinghua University

• Li Xuan

  College of Life Sciences, Zhejiang Sci-Tech University

• Zhang Xin

  School of Preclinical Medicine, Beijing University of Chinese Medicine

• Shi Long

  School of Life Science, Tsinghua University

• Sheng Qing

  College of Life Sciences, Zhejiang Sci-Tech University

• Yao Ling

  College of Biological and Environmental Engineering, Zhejiang University of Technology

• Shen Dong

  School of Life Science, Tsinghua University

• Park Yong-Doo

  Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University

• Lee Jinhyuk

  Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology

• Lee Jinhyuk

  Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology:Department of Bioinformatics, University of Sciences and Technology

• Zhang Qian

  School of Civil Engineering and Architecture, Wuhan University of Technology

• Zhou Hai-Meng

  School of Life Science, Tsinghua University:Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University

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• Effect of Ca^ on the activity and structure of α-glucosidase : Inhibition kinetics and molecular dynamics simulations(ENZYMOLOGY, PROTEIN ENGINEERING, AND ENZYME TECHNOLOGY)

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