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Hydrophobic Amino Acid and Single-Atom Substitutions Increase DNA Polymerase Selectivity

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2007

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Rudinger, Nicolas Z.

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https://doi.org/10.1016/j.chembiol.2006.11.016
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Chemistry & Biology. 2007, 14(2), pp. 185-194. ISSN 1074-5521. eISSN 1879-1301. Available under: doi: 10.1016/j.chembiol.2006.11.016

Zusammenfassung

DNA polymerase fidelity is of immense biological importance due to the fundamental requirement for accurate DNA synthesis in both replicative and repair processes. Subtle hydrogen-bonding networks between DNA polymerases and their primer/template substrates are believed to have impact on DNA polymerase selectivity. We show that deleting defined interactions of that kind by rationally designed hydrophobic substitution mutations can result in a more selective enzyme. Furthermore, a single-atom replacement within the DNA substrate through chemical modification, which leads to an altered acceptor potential and steric demand of the DNA substrate, further increased the selectivity of the developed systems. Accordingly, this study about the impact of hydrophobic alterations on DNA polymerase selectivity--enzyme and substrate wise--further highlights the relevance of shape complementary and polar interactions on DNA polymerase selectivity.

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540 Chemie

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ISO 690RUDINGER, Nicolas Z., Ramon KRANASTER, Andreas MARX, 2007. Hydrophobic Amino Acid and Single-Atom Substitutions Increase DNA Polymerase Selectivity. In: Chemistry & Biology. 2007, 14(2), pp. 185-194. ISSN 1074-5521. eISSN 1879-1301. Available under: doi: 10.1016/j.chembiol.2006.11.016
BibTex
@article{Rudinger2007-02Hydro-34120,
  year={2007},
  doi={10.1016/j.chembiol.2006.11.016},
  title={Hydrophobic Amino Acid and Single-Atom Substitutions Increase DNA Polymerase Selectivity},
  number={2},
  volume={14},
  issn={1074-5521},
  journal={Chemistry & Biology},
  pages={185--194},
  author={Rudinger, Nicolas Z. and Kranaster, Ramon and Marx, Andreas}
}
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