BIOMAT Database Logo BIOMAT Database Logo

Solution structure of duplex DNA containing an extrahelical abasic site analog determined by NMR spectroscopy and molecular dynamics. 1998

Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA.

Translesional DNA synthesis past abasic sites proceeds with the preferential incorporation of dAMP opposite the lesion and, depending on the sequence context, one or two base deletions. High-resolution NMR spectroscopy and molecular dynamics simulations were used to determine the three-dimensional structure of a DNA heteroduplex containing a synthetic abasic site (tetrahydrofuran) residue positioned in a sequence that promotes one base deletions. Analysis of NMR spectra indicates that the stem region of the duplex adopts a right-handed helical structure and the glycosidic torsion angle is in anti orientation for all residues. NOE interactions establish Watson-Crick alignments for all canonical base pairs of the duplex. Measurement of distance interactions at the lesion site shows the abasic residue excluded from the helix. Restrained molecular dynamics simulations generated three-dimensional models in excellent agreement with the spectroscopic data. These structures show a regular duplex region and a slight bend at the lesion site. The tetrahydrofuran residue extrudes from the helix and is highly flexible. The model reported here, in conjunction with a previous study performed on abasic sites, explains the structural bias of one-base deletion mutations.

UI MeSH Term Description Entries
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D009692 Nucleic Acid Heteroduplexes Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids. Heteroduplexes, Nucleic Acid,Heteroduplex DNA,Acid Heteroduplexes, Nucleic,DNA, Heteroduplex
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D005663 Furans Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran. Tetrahydrofurans
D019906 Nuclear Magnetic Resonance, Biomolecular NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope. Biomolecular Nuclear Magnetic Resonance,Heteronuclear Nuclear Magnetic Resonance,NMR Spectroscopy, Protein,NMR, Biomolecular,NMR, Heteronuclear,NMR, Multinuclear,Nuclear Magnetic Resonance, Heteronuclear,Protein NMR Spectroscopy,Biomolecular NMR,Heteronuclear NMR,Multinuclear NMR,NMR Spectroscopies, Protein,Protein NMR Spectroscopies,Spectroscopies, Protein NMR,Spectroscopy, Protein NMR

Related Publications

Z Lin, and K N Hung, and A P Grollman, and C de los Santos
An abasic site in DNA. Solution conformation determined by proton NMR and molecular mechanics calculations.
October 1987, Nucleic acids research,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Solution structure of an oligodeoxynucleotide duplex containing the exocyclic lesion 3,N4-etheno-2'-deoxycytidine opposite 2'-deoxyadenosine, determined by NMR spectroscopy and restrained molecular dynamics.
October 1996, Biochemistry,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Refined solution structure of a DNA heteroduplex containing an aldehydic abasic site.
September 1995, The Journal of biological chemistry,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Solution structure of a duplex DNA with an abasic site in a dA tract.
September 1997, Biochemistry,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Abasic frameshift in DNA. Solution conformation determined by proton NMR and molecular mechanics calculations.
March 1989, Biochemistry,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Solution structure of the Lewis x oligosaccharide determined by NMR spectroscopy and molecular dynamics simulations.
July 1992, Biochemistry,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Two-dimensional 1H and 31P NMR spectra and restrained molecular dynamics structure of an extrahelical adenosine tridecamer oligodeoxyribonucleotide duplex.
October 1989, Biochemistry,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
The solution structure of an oligonucleotide duplex containing a 2'-deoxyadenosine-3-(2-hydroxyethyl)- 2'-deoxyuridine base pair determined by NMR and molecular dynamics studies.
March 2002, Nucleic acids research,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics.
January 2024, Biophysical journal,
Z Lin, and K N Hung, and A P Grollman, and C de los Santos
Structure elucidation and 3D solution conformation of the antibiotic enduracidin determined by NMR spectroscopy and molecular dynamics.
August 2005, Magnetic resonance in chemistry : MRC,
Copied contents to your clipboard!