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.

Magnolol and Luteolin Inhibition of α-Glucosidase Activity: Kinetics and Type of Interaction Detected by In Vitro and In Silico Studies

“…These data indicate that the inhibitors quickly and spontaneously bind to the enzyme, deactivating its catalytic function. Furthermore, the kinetics of the interaction show that the process reaches an equilibrium state in a very short time, suggesting specific binding sites for inhibitors on α-glucosidase [23].…”

CdCl2 has zero-order kinetic cellular influx and induces cytotoxicity and genotoxicity at low concentrations in human leukocytes in vitro

“…The mechanism by which Cd 2+ induces cellular injuries appears to be supported, at least in part, by apoptotic pathways [3,12]. Furthermore, the potential injury caused by Cd 2+ appears to be associated with our own ability to induce protein denaturation and oxidative stress and decrease the enzymatic activity [13][14][15].…”