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Studies on the activation of isocitrate dehydrogenase kinase/phosphatase (AceK) by Mn2+ and Mg2.
Biometals. 2018 12; 31(6):991-1002.B

Abstract

Isocitrate dehydrogenase kinase/phosphatase (AceK) is a bifunctional enzyme with both kinase and phosphatase activities that are activated by Mg2+. We have studied the interactions of Mn2+and Mg2+ with AceK using isothermal titration calorimetry (ITC) combined with molecular docking simulations and show for the first time that Mn2+ also activates the enzyme activities. However, Mn2+ and Mg2+ exert their effects by different mechanisms. Although they have similar binding constants (of 1.11 × 105 and 0.98 × 105 M-1, respectively) for AceK and induce conformational changes of the enzyme, they do not compete for the same binding site. Instead Mn2+ appears to bind to the regulatory domain of AceK, and its effect is transmitted to the active site of the enzyme by the conformational change that it induces. The information in this study should be very useful for understanding the molecular mechanism underlying the interaction between AceK and metal ions, especially Mn2+ and Mg2+.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, People's Republic of China.Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, People's Republic of China.Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, People's Republic of China.Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, People's Republic of China. jgh982@bnu.edu.cn.Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing, 100875, People's Republic of China. weiq@bnu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30311020

Citation

Yin, Yanxia, et al. "Studies On the Activation of Isocitrate Dehydrogenase Kinase/phosphatase (AceK) By Mn2+ and Mg2." Biometals : an International Journal On the Role of Metal Ions in Biology, Biochemistry, and Medicine, vol. 31, no. 6, 2018, pp. 991-1002.
Yin Y, Gao Y, Li S, et al. Studies on the activation of isocitrate dehydrogenase kinase/phosphatase (AceK) by Mn2+ and Mg2. Biometals. 2018;31(6):991-1002.
Yin, Y., Gao, Y., Li, S., Jiang, G., & Wei, Q. (2018). Studies on the activation of isocitrate dehydrogenase kinase/phosphatase (AceK) by Mn2+ and Mg2. Biometals : an International Journal On the Role of Metal Ions in Biology, Biochemistry, and Medicine, 31(6), 991-1002. https://doi.org/10.1007/s10534-018-0144-0
Yin Y, et al. Studies On the Activation of Isocitrate Dehydrogenase Kinase/phosphatase (AceK) By Mn2+ and Mg2. Biometals. 2018;31(6):991-1002. PubMed PMID: 30311020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Studies on the activation of isocitrate dehydrogenase kinase/phosphatase (AceK) by Mn2+ and Mg2. AU - Yin,Yanxia, AU - Gao,Yadan, AU - Li,Shanze, AU - Jiang,Guohua, AU - Wei,Qun, Y1 - 2018/10/12/ PY - 2018/07/05/received PY - 2018/09/22/accepted PY - 2018/10/13/pubmed PY - 2019/9/4/medline PY - 2018/10/13/entrez KW - AceK KW - Activation KW - Binding KW - ITC KW - Kinase KW - Phosphatase SP - 991 EP - 1002 JF - Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine JO - Biometals VL - 31 IS - 6 N2 - Isocitrate dehydrogenase kinase/phosphatase (AceK) is a bifunctional enzyme with both kinase and phosphatase activities that are activated by Mg2+. We have studied the interactions of Mn2+and Mg2+ with AceK using isothermal titration calorimetry (ITC) combined with molecular docking simulations and show for the first time that Mn2+ also activates the enzyme activities. However, Mn2+ and Mg2+ exert their effects by different mechanisms. Although they have similar binding constants (of 1.11 × 105 and 0.98 × 105 M-1, respectively) for AceK and induce conformational changes of the enzyme, they do not compete for the same binding site. Instead Mn2+ appears to bind to the regulatory domain of AceK, and its effect is transmitted to the active site of the enzyme by the conformational change that it induces. The information in this study should be very useful for understanding the molecular mechanism underlying the interaction between AceK and metal ions, especially Mn2+ and Mg2+. SN - 1572-8773 UR - https://www.unboundmedicine.com/medline/citation/30311020/Studies_on_the_activation_of_isocitrate_dehydrogenase_kinase/phosphatase__AceK__by_Mn2+_and_Mg2_ L2 - https://doi.org/10.1007/s10534-018-0144-0 DB - PRIME DP - Unbound Medicine ER -