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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Chemistry Faculty Publications

2013

Desolvation energies;DNA polymerase;mutagenesis;non-natural nucleotides;translesion DNA synthesis

Articles 1 - 1 of 1

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Insights Into The Roles Of Desolvation And Π-Electron Interactions During Dna Polymerization, Edward A. Motea, Irene Lee, Anthony J. Berdis Mar 2013

Insights Into The Roles Of Desolvation And Π-Electron Interactions During Dna Polymerization, Edward A. Motea, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

This report describes the use of several isosteric non-natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π-electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high- and low-fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high-fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low-fidelity HIV-1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non-natural ...