title: Structure of DNA sequence d-TGATCA by two-dimensional nuclear magnetic resonance spectroscopy and restrained molecular dynamics.
abstract: The 5' d-TpG 3' element is a part of DNA sequences involved in regulation of gene expression and is also a site for intercalation of several anticancer drugs. Solution conformation of DNA duplex d-TGATCA containing this element has been investigated by two-dimensional NMR spectroscopy. Using a total of 12 torsional angles and 121 distance constraints, structural refinement has been carried out by restrained molecular dynamics (rMDs) in vacuum up to 100 ps. The structure is characterized by a large positive roll at TpG/CpA base pair step and large negative propeller twist for AT and TA base pairs. The backbone torsional angle, gamma(O5'-C5'-C4'-C3'), of T1 residue adopts a trans-conformation which is corroborated by short intra nucleotide T1H6-T1H5' (3.7A) distance in nuclear overhauser effect spectroscopy (NOESY) spectra while the backbone torsional angle, beta(P-O5'-C5'-C4'), exists in trans as well as gauche state for T1 and C5 residues. There is evidence of significant flexibility of the sugar-phosphate backbone with rapid inter-conversion between two different conformers at TpG/CpA base pair step. The base sequence dependent variations and local structural heterogeneity have important implications in specific recognition of DNA by ligands.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Roorkee, 247 667. ritubarthwal@yaoo.co.in
authors.forename: Ritu
authors.initials: R
authors.lastname: Barthwal
authors.forename: Pamita
authors.initials: P
authors.lastname: Awasthi
authors.lastname: Monica
authors.forename: Manpreet
authors.initials: M
authors.lastname: Kaur
authors.forename: Uma
authors.initials: U
authors.lastname: Sharma
authors.forename: Nandana
authors.initials: N
authors.lastname: Srivastava
authors.forename: S K
authors.initials: SK
authors.lastname: Barthwal
authors.forename: Girjesh
authors.initials: G
authors.lastname: Govil
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA