title: Pairing geometry of the hydrophobic thymine analogue 2,4-difluorotoluene in duplex DNA as analyzed by X-ray crystallography.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Pallan
authors.forename: Martin
authors.initials: M
authors.lastname: Egli
mesh_terms: D001407:Bacillus / Q000201:enzymology; D020029:Base Pairing; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D016914:Ribonuclease H / Q000378:metabolism; D013941:Thymine / Q000031:analogs & derivatives*; D014050:Toluene / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D014050:Toluene; C110527:difluorotoluene; D004247:DNA; D016914:Ribonuclease H; D013941:Thymine
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