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Inhibition of CK2 Activity by TCDD via Binding to ATP-competitive Binding Site of Catalytic Subunit: Insight from Computational Studies 被引量:1

Inhibition of CK2 Activity by TCDD via Binding to ATP-competitive Binding Site of Catalytic Subunit: Insight from Computational Studies
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摘要 Alternative mechanisms of toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD), instead of the binding to aryl hydrocarbon receptor(AhR), have been taken into consideration. It has been recently shown that TCDD reduces rapidly the activity of CK2(casein kinase II) both in vivo and in vitro. It is found that TCDD has high molecular similarities to the known inhibitors of CK2 catalytic subunit(CK2a). This suggests that TCDD could also be an ATP-competitive inhibitor of CK2a. In this work, docking TCDD to CK2 was carried out based on the two structures of CK2a from maize and human, respectively. The binding free energies of the predicted CK2a-TCDD complexes estimated by the molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method are from -85.1 kJ/mol to -114.3 kJ/mol for maize and are from -96.1 kJ/mol to -118.2 kJ/mol for human, which are comparable to those estimated for the known inhibitor and also ATP with CK2a. The energetic analysis also reveals that the van der Waals interaction is the dominant contribution to the binding free energy. These results are also useful for designing new drugs for a target of overexpressing CK2 in cancers. Alternative mechanisms of toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD), instead of the binding to aryl hydrocarbon receptor(AhR), have been taken into consideration. It has been recently shown that TCDD reduces rapidly the activity of CK2(casein kinase II) both in vivo and in vitro. It is found that TCDD has high molecular similarities to the known inhibitors of CK2 catalytic subunit(CK2a). This suggests that TCDD could also be an ATP-competitive inhibitor of CK2a. In this work, docking TCDD to CK2 was carried out based on the two structures of CK2a from maize and human, respectively. The binding free energies of the predicted CK2a-TCDD complexes estimated by the molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method are from -85.1 kJ/mol to -114.3 kJ/mol for maize and are from -96.1 kJ/mol to -118.2 kJ/mol for human, which are comparable to those estimated for the known inhibitor and also ATP with CK2a. The energetic analysis also reveals that the van der Waals interaction is the dominant contribution to the binding free energy. These results are also useful for designing new drugs for a target of overexpressing CK2 in cancers.
出处 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2013年第2期299-306,共8页 高等学校化学研究(英文版)
基金 Supported by the International Science and Technology Cooperation Program of China(No.2010DFA31710), the National Natural Science Foundation of China(No.10974008), the Doctoral Fund of Innovation from Beijing University of Technology (China), and the Project from the Italian Association for Cancer Research(No.IG10412).
关键词 Casein kinase II DIOXIN Inhibitor Modeling Binding free energy Casein kinase II Dioxin Inhibitor Modeling Binding free energy
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  • 1Pitot H. c., Goldsworthy T., Campbell H. A., Poland A., Cancer Res., 1980,40,3616.
  • 2Poland A, Knutson J. C., Annu. Rev. Pharmacol. Toxicol., 1982, 22, 517.
  • 3Mandai P. K., J. Compo Physiol. E, 2005, 175, 221.
  • 4Huff J., Lucier G., Tritscher A, Annu. Rev. Pharmacol. Toxicol., 1994,34,343.
  • 5Kamath A 8., Xu H., Nagarkatti P. S., Nagarkatti M., Toxicol. Appl. Pharmacol., 1997, 142, 367.
  • 6Pryputniewicz S. J., Nagarkatti M., Nagarkatti P. S., Toxicology, 1998, 129,211.
  • 7Lai Z. w., Fiore N. C., Gasiewicz T. A, Silverstone A E., Toxicol. Appl. Pharm., 1998, 149, 167.
  • 8Fernandez-Salguero P. M., Hilbert D. M., Rudikoff S., Ward J. M., Gonzalez E J., Toxicol. Appl. Pharmacol., 1996, 140, 173.
  • 9Dietrich C., Kaina R, Carcinogenesis, 2010, 31, 1319.
  • 10Hankinson O., Annu. Rev. Pharmacol. Toxicol., 1995, 35, 307.

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