In a recent article (
1
), the authors examined biophysical characteristics in the interaction between methylated DNA and ZBTB38 protein, which possesses five zinc finger domains (ZFs 6–10) in the C-terminal region. While the authors identified that ZFs 6–9 were minimal structural elements for high-affinity DNA binding, the role of ZF 10 remained inconclusive. Here, we show that the binding data shown in Fig. 1 of the paper can be used to predict the role of ZF 10 in regard to binding to methylated DNA with an algebraic technique of solving a system of linear equations ().Fig. 1 of the paper reports dissociation constants (KD) of 5.3 nm, 5.0 nm, and 40.6 nm for ZFs 6–10, ZFs 6–9, and ZFs 7–10, respectively. From this information, a system of linear equations of binding affinity (ΔG0) with three unknowns can be established using the thermodynamic relation, ΔG0 = RT × ln KD (
3
), with an assumption of additivity in the binding (4
).
- ZFs 6–10: ΔG0(ZF 6) + ΔG0(ZFs 7–9) + ΔG0(ZF 10) = −46.7 kJ/mol
- ZFs 6–9: ΔG0(ZF 6) + ΔG0(ZFs 7–9) = −46.9 kJ/mol
- ZFs 7–10: ΔG0(ZFs 7–9) + ΔG0(ZF 10) = −41.7 kJ/mol
By solving the three equations, we obtained that ΔG0(ZF 6) = −5.0 kJ/mol, ΔG0(ZF 7–9) = −41.9 kJ/mol, and ΔG0(ZF 10) = 0.2 kJ/mol. Our calculation clearly suggests that ZF 10 in ZBTB38 protein does not contribute to binding affinity in agreement with the speculation made in the paper (
1
).References
- Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38.J. Biol. Chem. 2018; 293 (30355731): 19835-19843
- Precalculus: A Prelude to Calculus. Wiley, Hoboken, NJ2012
- Physical Chemistry for the Chemical and Biological Science. University Science Books, Sausalito, CA2000
- Thermodynamic analysis of additivity between the heavy and light chains in affinity maturation of an antibody.Mol. Immunol. 2008; 45 (17707510): 304-305
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Published online: January 01, 2019
Edited by Karin Musier-ForsythFootnotes
These authors declare that they have no conflicts of interest with the contents of this article.
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