DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs

Natasha Paul, Vishal C. Nashine, Geoffrey Hoops, Peiming Zhang, Jie Zhou, Donald E. Bergstrom, V. Jo Davisson

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The development of novel artificial nucleobases and detailed X-ray crystal structures for primer/template/DNA polymerase complexes provide opportunities to assess DNA-protein interactions that dictate specificity. Recent results have shown that base pair shape recognition in the context of DNA polymerase must be considered a significant component. The isosteric azole carboxamide nucleobases (compounds 1-5; Figure 1) differ only in the number and placement of nitrogen atoms within a common shape and therefore present unique electronic distributions that are shown to dictate the selectivity of template-directed nucleotide incorporation by DNA polymerases. The results demonstrate how nucleoside triphosphate substrate selection by DNA polymerase is a complex phenomenon involving electrostatic interactions in addition to hydrogen bonding and shape recognition. These azole nucleobase analogs offer unique molecular tools for probing nonbonded interactions dictating substrate selection and fidelity of DNA polymerases.

Original languageEnglish (US)
Pages (from-to)815-825
Number of pages11
JournalChemistry and Biology
Volume10
Issue number9
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

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DNA-Directed DNA Polymerase
Azoles
Substrates
Hydrogen Bonding
Coulomb interactions
Static Electricity
Nucleosides
Base Pairing
Hydrogen bonds
Nitrogen
Nucleotides
Crystal structure
X-Rays
X rays
Atoms
DNA
Proteins

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Paul, N., Nashine, V. C., Hoops, G., Zhang, P., Zhou, J., Bergstrom, D. E., & Davisson, V. J. (2003). DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs. Chemistry and Biology, 10(9), 815-825. https://doi.org/10.1016/j.chembiol.2003.08.008

DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs. / Paul, Natasha; Nashine, Vishal C.; Hoops, Geoffrey; Zhang, Peiming; Zhou, Jie; Bergstrom, Donald E.; Davisson, V. Jo.

In: Chemistry and Biology, Vol. 10, No. 9, 01.09.2003, p. 815-825.

Research output: Contribution to journalArticle

Paul, N, Nashine, VC, Hoops, G, Zhang, P, Zhou, J, Bergstrom, DE & Davisson, VJ 2003, 'DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs', Chemistry and Biology, vol. 10, no. 9, pp. 815-825. https://doi.org/10.1016/j.chembiol.2003.08.008
Paul, Natasha ; Nashine, Vishal C. ; Hoops, Geoffrey ; Zhang, Peiming ; Zhou, Jie ; Bergstrom, Donald E. ; Davisson, V. Jo. / DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs. In: Chemistry and Biology. 2003 ; Vol. 10, No. 9. pp. 815-825.
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