title: Effect of Cadmium Ion on alpha-Glucosidase: An Inhibition Kinetics and Molecular Dynamics Simulation Integration Study.
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 Cd(2+) based on α-glucosidase activity and conformational changes. We studied Cd(2+)-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 Cd(2+) in a reversibly binding behavior, and Cd(2+) binding induced a non-competitive type of inhibition reaction (the K i was calculated as 0.3863 ± 0.033 mM). Cd(2+) 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 Cd(2+) induced in a depletion of secondary structure by docking Cd(2+) near the saccharides degradation at the active site, suggesting that Cd(2+) modulating enzyme denaturation. The present study elucidated that the binding of Cd(2+) triggers conformational changes of α-glucosidase as well as inactivates catalytic function, and thus suggests an explanation of the deleterious effects of Cd(2+) on α-glucosidase.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea.|Department of Nanobiotechnology and Bioinformatics, University of Sciences and Technology, Daejeon, 305-350, Korea.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing, 314006, People's Republic of China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Lü
authors.affiliation: Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing, 314006, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Mu
authors.affiliation: 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.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Yue
authors.affiliation: Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing, 314006, People's Republic of China.
authors.forename: Yong-Doo
authors.initials: YD
authors.lastname: Park
authors.affiliation: 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. zhuomingye@hotmail.com.
authors.forename: Zhuo-Ming
authors.initials: ZM
authors.lastname: Ye
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D065089:Glycoside Hydrolase Inhibitors / Q000633:toxicity*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation / Q000187:drug effects; D011489:Protein Denaturation / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*; D000520:alpha-Glucosidases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004785:Environmental Pollutants; D065089:Glycoside Hydrolase Inhibitors; D002104:Cadmium; D000520:alpha-Glucosidases
keywords: Cd2+; Denaturation; Inhibition kinetics; Molecular dynamics; α-Glucosidase