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Evaluating substrate specificity of glutathione peroxidase mimic by molecular dynamics simulations and kinetics

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Abstract

The substrate specificities of glutathione peroxidase (GPX) mimic, 6,6′-ditellurobis(6-deoxy-β-cyclodextrin) (6-TeCD), for three hydroperoxides (ROOH), H2O2, tert-butyl hydroperoxide (t-BuOOH) and cumene hydroperoxide (CuOOH), are investigated through molecular dynamics (MD) simulations. The most stable conformations and the total interaction energies of complex of 6-TeCD with ROOH are used to evaluate the substrate specificity of 6-TeCD. The steady-state kinetics of 6-TeCD is studied and the Michaelis-Menten constant (K m) and second-order rate constant k max/K ROOH show that 6-TeCD displays different affinity and specificity to ROOH. These results of experiments are well consistent with ones obtained by MD simulations, indicating that MD simulations could be applied to evaluation substrate specificity of small-molecule enzyme mimics.

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Abbreviations

GPX:

Glutathione peroxidase

GSH:

Glutathione

t-BuOOH:

Tert-butyl hydroperoxide

CuOOH:

Cumenyl hydroperoxide

Ebselen:

2-Phenyl-1,2-benzoisoselenazol-3(2H)-one

NADPH:

β-Nicotinamide adenine dinucleotide phosphate

β-CD:

β-Cyclodextrin

PBS:

Potassium phosphate buffer

MD:

Molecular dynamics

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Acknowledgements

This research is supported by Natural Science Foundation of China (Project No. 20572035) and Jilin University for financial support.

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Authors and Affiliations

  1. Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2519 Jiefang Road, Changchun, 130021, P.R. China

    Shao-Wu Lv, Ying Mu, Xiao-Guang Wang, Yue-Tong Ji & Gui-Min Luo

  2. State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, P.R. China

    Qing-Chuan Zheng

  3. Key Laboratory for Supramolecular Structure and Materials of the Ministry of Education, Jilin University, Changchun, 130012, P.R. China

    Jun-Qiu Liu & Jia-Cong Shen

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  1. Shao-Wu Lv
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  2. Qing-Chuan Zheng
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Correspondence to Gui-Min Luo.

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Lv, SW., Zheng, QC., Mu, Y. et al. Evaluating substrate specificity of glutathione peroxidase mimic by molecular dynamics simulations and kinetics. J Incl Phenom Macrocycl Chem 60, 139–144 (2008). https://doi.org/10.1007/s10847-007-9362-8

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  • DOI: https://doi.org/10.1007/s10847-007-9362-8

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