Publication Abstract from PubMed
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.
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 Aug 17. PMID:19685868[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
