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The 8-oxo-dGTP interaction with human DNA polymerase β: two patterns of ligand behavior

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Abstract

The behavior of 8-oxo-dGTP molecule in the area of the active site of human DNA polymerase β was investigated using molecular dynamics (MD) calculation. The principle phenomenon revealed as investigation results is existence of two cardinally different models of behavior inherent in 8-oxo-dGTP molecule. In the several cases, 8-oxo-dGTP stably stays in DNA polymerase active site, “keeps in touch” with template nucleotide and maintains the hydrogen bonds with it (stable behavior). In other cases, the ligand molecules lose the connections with template dA and start to migrate inside of enzyme space (migrate behavior). The 8-oxo-dGTP in cases of migrate behavior is still in DNA polymerase space at least over 100 ns and prevents transit of DNA polymerase from closed to open conformation as well as the further binding of incoming dNTP. This observation lets a possibility to consider it as natural inhibitor/regulator of DNA pol β activity.

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Acknowledgments

Author thanks the Extreme Science and Engineering Discovery Environment (XSEDE) for the award allocation number TG-DMR110088.

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  1. Department of Molecular Biotechnology and Bioinformatics, Taras Shevchenko National University of Kyiv, Volodymyrska str. 60, Kiev, 01601, Ukraine

    A. Yu. Nyporko

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Correspondence to A. Yu. Nyporko.

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Nyporko, A.Y. The 8-oxo-dGTP interaction with human DNA polymerase β: two patterns of ligand behavior. Struct Chem 27, 175–183 (2016). https://doi.org/10.1007/s11224-015-0691-8

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