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Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA

School of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5142;
Received: 2 September 2019 / Revised: 3 October 2019 / Accepted: 12 October 2019 / Published: 17 October 2019
(This article belongs to the Section Biochemistry)
The well-known mismatch repair (MMR) machinery, MutS/MutL, is absent in numerous Archaea and some Bacteria. Recent studies have shown that EndoMS/NucS has the ability to cleave double-stranded DNA (dsDNA) containing a mismatched base pair, which suggests a novel mismatch repair process. However, the recognition mechanism and the binding process of EndoMS/NucS in the MMR pathway remain unclear. In this study, we investigate the binding dynamics of EndoMS/NucS to mismatched dsDNA and its energy as a function of the angle between the two C-terminal domains of EndoMS/NucS, through molecular docking and extensive molecular dynamics (MD) simulations. It is found that there exists a half-open transition state corresponding to an energy barrier (at an activation angle of approximately 80 ) between the open state and the closed state, according to the energy curve. When the angle is larger than the activation angle, the C-terminal domains can move freely and tend to change to the open state (local energy minimum). Otherwise, the C-terminal domains will interact with the mismatched dsDNA directly and converge to the closed state at the global energy minimum. As such, this two-state system enables the exposed N-terminal domains of EndoMS/NucS to recognize mismatched dsDNA during the open state and then stabilize the binding of the C-terminal domains of EndoMS/NucS to the mismatched dsDNA during the closed state. We also investigate how the EndoMS/NucS recognizes and binds to mismatched dsDNA, as well as the effects of K + ions. The results provide insights into the recognition and binding mechanisms of EndoMS/NucS to mismatched dsDNA in the MMR pathway. View Full-Text
Keywords: protein–DNA interactions; mismatch repair; EndoMS/NucS; molecular dynamics protein–DNA interactions; mismatch repair; EndoMS/NucS; molecular dynamics
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Zhang, Y.; Huang, S. Exploring the Binding Mechanism and Dynamics of EndoMS/NucS to Mismatched dsDNA. Int. J. Mol. Sci. 2019, 20, 5142.

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