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Stereoselectivity of chalcone isomerase with chalcone derivatives: a computational study

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Abstract

Chalcone isomerase (CHI) catalyzes the intramolecular cyclization of chalcones into flavonoids. The activity of CHI is essential for the biosynthesis of flavonoids precursors of floral pigments and phenylpropanoid plant defense compounds. In the present study, we explored the detailed binding structures and binding free energies for two different active site conformations of CHI with s-cis/s-trans conformers of three chalcone compounds by performing molecular dynamics (MD) simulations and binding free energy calculations. The computational results indicate that s-cis/s-trans conformers of chalcone compounds are orientated in the similar binding position in the active site of CHI and stabilized by the different first hydrogen bond network and the same second hydrogen bond network. The first hydrogen bond network results in much lower binding affinity of s-trans conformer of chalcone compound with CHI than that of s-cis conformer. The conformational change of the active site residue T48 from indirectly interacting with the substrate via the second hydrogen bond network to directly forming the hydrogen bond with the substrates cannot affect the binding mode of both conformers of chalcone compounds, but remarkably improves the binding affinity. These results show that CHI has a strong stereoselectivity. The calculated binding free energies for three chalcone compounds with CHI are consistent with the experimental activity data. In addition, several valuable insights are suggested for future rational design and discovery of high-efficiency mutants of CHI.

Stereoselectivity of chalcone isomerase with chalcone derivatives

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Acknowledgments

This work was supported by the Major State Basic Research Development Programs of China (2011CBA00701, 2012CB721003), the National Natural Science Foundation of China (20973049), the Doctoral Foundation by the Ministry of Education of China (20112303110005), the SF for leading experts in academe of Harbin of China (2011RFJGS026), the Science Funds for Distinguished Young Scholar of Heilongjiang Province (JC201206), and the Fundamental Research Funds for the Central Universities (Grant No. HIT. NSRIF. 2013056).

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Authors and Affiliations

  1. Academy of Fundamental and Interdisciplinary Science, Harbin Institute of Technology, Harbin, 150080, People’s Republic of China

    Yuan Yao & Ze-Sheng Li

  2. College of Chemical and Environmental Engineering, Harbin University of Science and Technology, Harbin, 150080, People’s Republic of China

    Hui Zhang

  3. Key Laboratory of Cluster Science of Ministry of Education & School of Chemistry, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China

    Ze-Sheng Li

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  1. Yuan Yao
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Correspondence to Hui Zhang or Ze-Sheng Li.

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Yao, Y., Zhang, H. & Li, ZS. Stereoselectivity of chalcone isomerase with chalcone derivatives: a computational study. J Mol Model 19, 4753–4761 (2013). https://doi.org/10.1007/s00894-013-1975-9

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  • DOI: https://doi.org/10.1007/s00894-013-1975-9

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