title: New insights into Hoogsteen base pairs in DNA duplexes from a structure-based survey.
abstract: Hoogsteen (HG) base pairs (bps) provide an alternative pairing geometry to Watson-Crick (WC) bps and can play unique functional roles in duplex DNA. Here, we use structural features unique to HG bps (syn purine base, HG hydrogen bonds and constricted C1'-C1' distance across the bp) to search for HG bps in X-ray structures of DNA duplexes in the Protein Data Bank. The survey identifies 106 A•T and 34 G•C HG bps in DNA duplexes, many of which are undocumented in the literature. It also uncovers HG-like bps with syn purines lacking HG hydrogen bonds or constricted C1'-C1' distances that are analogous to conformations that have been proposed to populate the WC-to-HG transition pathway. The survey reveals HG preferences similar to those observed for transient HG bps in solution by nuclear magnetic resonance, including stronger preferences for A•T versus G•C bps, TA versus GG steps, and also suggests enrichment at terminal ends with a preference for 5'-purine. HG bps induce small local perturbations in neighboring bps and, surprisingly, a small but significant degree of DNA bending (∼14°) directed toward the major groove. The survey provides insights into the preferences and structural consequences of HG bps in duplex DNA.
authors: Department of Biochemistry, Duke University, Durham, NC 27710, USA.
authors: Huiqing
authors: H
authors: Zhou
authors: Department of Biochemistry, Duke University, Durham, NC 27710, USA.
authors: Bradley J
authors: BJ
authors: Hintze
authors: Department of Biochemistry, Duke University, Durham, NC 27710, USA.
authors: Isaac J
authors: IJ
authors: Kimsey
authors: Department of Biochemistry, Duke University, Durham, NC 27710, USA.
authors: Bharathwaj
authors: B
authors: Sathyamoorthy
authors: Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
authors: Shan
authors: S
authors: Yang
authors: Department of Biochemistry, Duke University, Durham, NC 27710, USA.
authors: Jane S
authors: JS
authors: Richardson
authors: Department of Biochemistry, Duke University, Durham, NC 27710, USA Department of Chemistry, Duke University, Durham, NC 27708, USA hashim.al.hashimi@duke.edu.
authors: Hashim M
authors: HM
authors: Al-Hashimi
mesh_terms: D020029:Base Pairing; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA