title: A Hoogsteen base pair embedded in undistorted B-DNA.
abstract: Hoogsteen base pairs within duplex DNA typically are only observed in regions containing significant distortion or near sites of drug intercalation. We report here the observation of a Hoogsteen base pair embedded within undistorted, unmodified B-DNA. The Hoogsteen base pair, consisting of a syn adenine base paired with an anti thymine base, is found in the 2.1 A resolution structure of the MATalpha2 homeodomain bound to DNA in a region where a specifically and a non-specifically bound homeodomain contact overlapping sites. NMR studies of the free DNA show no evidence of Hoogsteen base pair formation, suggesting that protein binding favors the transition from a Watson-Crick to a Hoogsteen base pair. Molecular dynamics simulations of the homeodomain-DNA complex support a role for the non-specifically bound protein in favoring Hoogsteen base pair formation. The presence of a Hoogsteen base pair in the crystal structure of a protein-DNA complex raises the possibility that Hoogsteen base pairs could occur within duplex DNA and play a hitherto unrecognized role in transcription, replication and other cellular processes.
authors.affiliation: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Aishima
authors.forename: Rossitza K
authors.initials: RK
authors.lastname: Gitti
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Noah
authors.forename: Hin Hark
authors.initials: HH
authors.lastname: Gan
authors.forename: Tamar
authors.initials: T
authors.lastname: Schlick
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wolberger
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D004247:DNA