Pairing geometry of the hydrophobic thymine analogue 2,4-difluorotoluene in duplex DNA as analyzed by X-ray crystallography.

Pallan PS, Egli M
J Am Chem Soc. 2009 131 (35): 12548-9

PMID: 19685868 · PMCID: PMC2757930 · DOI:10.1021/ja905739j

Certain DNA polymerases (pols) were found to efficiently insert A opposite the hydrophobic T isostere 2,4-difluorotoluene (F) and vice versa, resulting in the widely held belief that some pols rely on shape rather than H-bonding for accurate replication. Using X-ray crystallography we have analyzed the geometry of F:A pairs in duplex DNA and observed a distance between fluorine and the exocyclic amino group of A that is consistent with a H-bond, thus challenging the assumption that the F analogue is unable to engage in H-bonding as well as the steric hypothesis of DNA replication. Therefore, shape and H-bonding are inherently related, and steric constraints at a pol active site, or conferred by stacking or the DNA backbone conformation, may enable H-bonding by F.

MeSH Terms (10)

Bacillus Base Pairing Base Sequence Crystallography, X-Ray DNA Hydrophobic and Hydrophilic Interactions Models, Molecular Ribonuclease H Thymine Toluene

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