Flexible 5-guanidino-4-nitroimidazole DNA lesions: structures and thermodynamics.

5-Guanidino-4-nitroimidazole (NI), derived from guanine oxidation by reactive oxygen and nitrogen species, contains an unusual flexible ring-opened structure, with nitro and guanidino groups which possess multiple hydrogen bonding capabilities. In vitro primer extension experiments with bacterial and mammalian polymerases show that NI incorporates C as well as A and G opposite the lesion, depending on the polymerase. To elucidate structural and thermodynamic properties of the mutagenic NI lesion, we have investigated the structure of the modified base itself and the NI-containing nucleoside with high-level quantum mechanical calculations and have employed molecular modeling and molecular dynamics simulations in solution for the lesion in B-DNA duplexes, with four partner bases opposite the NI. Our results show that NI adopts a planar structure at the damaged base level. However, in the nucleoside and in DNA duplexes, steric hindrance between the guanidino group and its linked sugar causes NI to be nonplanar. The NI lesion can adopt both syn and anti conformations on the DNA duplex level, with the guanidino group positioned in the DNA major and minor grooves, respectively; the specific preference depends on the partner base. On the basis of hydrogen bonding and stacking interactions, groove dimensions, and bending, we find that the least distorted NI-modified duplex contains partner C, consistent with observed incorporation of C opposite NI. However, hydrogen bonding interactions between NI and partner G or A are also found, which would be compatible with the observed mismatches.

[1]  Stephen Neidle,et al.  Principles of nucleic acid structure , 2007 .

[2]  S. Broyde,et al.  Structural and thermodynamic features of spiroiminodihydantoin damaged DNA duplexes. , 2005, Biochemistry.

[3]  N. Geacintov,et al.  Combination of nitrogen dioxide radicals with 8-oxo-7,8-dihydroguanine and guanine radicals in DNA: oxidation and nitration end-products. , 2005, Journal of the American Chemical Society.

[4]  S. Pervaiz,et al.  Reactive oxygen species and the mitochondrial signaling pathway of cell death. , 2005, Histology and histopathology.

[5]  William L. Neeley,et al.  Urea lesion formation in DNA as a consequence of 7,8-dihydro-8-oxoguanine oxidation and hydrolysis provides a potent source of point mutations. , 2005, Chemical research in toxicology.

[6]  Christopher J. Rhodes,et al.  Role of oxygen radicals in DNA damage and cancer incidence , 2004, Molecular and Cellular Biochemistry.

[7]  William L. Neeley,et al.  In Vivo Bypass Efficiencies and Mutational Signatures of the Guanine Oxidation Products 2-Aminoimidazolone and 5-Guanidino-4-nitroimidazole* , 2004, Journal of Biological Chemistry.

[8]  M. Evans,et al.  Oxidative DNA damage and disease: induction, repair and significance. , 2004, Mutation research.

[9]  N. Geacintov,et al.  Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping* , 2004, Journal of Biological Chemistry.

[10]  Junmei Wang,et al.  Development and testing of a general amber force field , 2004, J. Comput. Chem..

[11]  T. Ozben,et al.  Reactive oxygen and nitrogen species in Alzheimer's disease. , 2004, Current Alzheimer research.

[12]  M. Greenberg.  In vitro and in vivo effects of oxidative damage to deoxyguanosine. , 2004, Biochemical Society transactions.

[13]  William L. Neeley,et al.  Efficient synthesis of DNA containing the guanine oxidation-nitration product 5-guanidino-4-nitroimidazole: generation by a postsynthetic substitution reaction. , 2004, Organic letters.

[14]  J. Klaunig,et al.  The role of oxidative stress in carcinogenesis. , 2004, Annual review of pharmacology and toxicology.

[15]  K. Utsumi,et al.  Mitochondrial generation of reactive oxygen species and its role in aerobic life. , 2003, Current medicinal chemistry.

[16]  I. Schlichting,et al.  Structural Basis for the Specificity of the Nitric-oxide Synthase Inhibitors W1400 and Nω-Propyl-l-Arg for the Inducible and Neuronal Isoforms* , 2003, Journal of Biological Chemistry.

[17]  N. Geacintov,et al.  Oxidative generation of guanine radicals by carbonate radicals and their reactions with nitrogen dioxide to form site specific 5-guanidino-4-nitroimidazole lesions in oligodeoxynucleotides. , 2003, Chemical research in toxicology.

[18]  Federico V Pallardó,et al.  The role of mitochondrial oxidative stress in aging. , 2003, Free radical biology & medicine.

[19]  M. Evans,et al.  Oxidative DNA damage: mechanisms, mutation, and disease , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  D. Patel,et al.  Simulating structural and thermodynamic properties of carcinogen-damaged DNA. , 2003, Biophysical journal.

[21]  C. Harris,et al.  Radical causes of cancer , 2003, Nature Reviews Cancer.

[22]  T. Buterin,et al.  Role of base sequence context in conformational equilibria and nucleotide excision repair of benzo[a]pyrene diol epoxide-adenine adducts. , 2003, Biochemistry.

[23]  B. Van Houten,et al.  Mitochondrial DNA repair and aging. , 2002, Mutation research.

[24]  P. Jaruga,et al.  Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome. , 2002, Free radical biology & medicine.

[25]  Roger A. Jones,et al.  Peroxynitrite-induced reactions of synthetic oligo 2'-deoxynucleotides and DNA containing guanine: formation and stability of a 5-guanidino-4-nitroimidazole lesion. , 2002, Biochemistry.

[26]  Santanu K. Mishra,et al.  An ab initio theoretical study of electronic structure and properties of 2′‐deoxyguanosine in gas phase and aqueous media , 2002, J. Comput. Chem..

[27]  S. Tannenbaum,et al.  Oxidation of 7,8-dihydro-8-oxoguanine affords lesions that are potent sources of replication errors in vivo. , 2002, Biochemistry.

[28]  Peter A. Kollman,et al.  Computational alanine scanning of the 1:1 human growth hormone–receptor complex , 2002, J. Comput. Chem..

[29]  S. Tannenbaum,et al.  A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine. , 2001, Journal of the American Chemical Society.

[30]  T. Lindahl,et al.  Age-related and tissue-specific accumulation of oxidative DNA base damage in 7,8-dihydro-8-oxoguanine-DNA glycosylase (Ogg1) deficient mice. , 2001, Carcinogenesis.

[31]  Zhongmao Guo,et al.  Does oxidative damage to DNA increase with age? , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Broyde,et al.  Stereochemical, structural, and thermodynamic origins of stability differences between stereoisomeric benzo[a]pyrene diol epoxide deoxyadenosine adducts in a DNA mutational hot spot sequence. , 2001, Journal of the American Chemical Society.

[33]  C. Burrows,et al.  Characterization of hydantoin products from one-electron oxidation of 8-oxo-7,8-dihydroguanosine in a nucleoside model. , 2001, Chemical research in toxicology.

[34]  P. Kollman,et al.  Use of MM-PBSA in reproducing the binding free energies to HIV-1 RT of TIBO derivatives and predicting the binding mode to HIV-1 RT of efavirenz by docking and MM-PBSA. , 2001, Journal of the American Chemical Society.

[35]  S R Tannenbaum,et al.  Spiroiminodihydantoin is the major product of the 8-oxo-7,8-dihydroguanosine reaction with peroxynitrite in the presence of thiols and guanosine photooxidation by methylene blue. , 2001, Organic letters.

[36]  N. Holbrook,et al.  Oxidants, oxidative stress and the biology of ageing , 2000, Nature.

[37]  P A Kollman,et al.  Free energy calculations on dimer stability of the HIV protease using molecular dynamics and a continuum solvent model. , 2000, Journal of molecular biology.

[38]  P. Kollman,et al.  Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. , 2000, Accounts of chemical research.

[39]  Junmei Wang,et al.  How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? , 2000, J. Comput. Chem..

[40]  M R Lee,et al.  Use of MM‐PB/SA in estimating the free energies of proteins: Application to native, intermediates, and unfolded villin headpiece , 2000, Proteins.

[41]  Nicolas Leulliot,et al.  Ground-State Properties of Nucleic Acid Constituents Studied by Density Functional Calculations. 3. Role of Sugar Puckering and Base Orientation on the Energetics and Geometry of 2‘-Deoxyribonucleosides and Ribonucleosides , 2000 .

[42]  P. Kollman,et al.  Investigating the binding specificity of U1A-RNA by computational mutagenesis. , 2000, Journal of molecular biology.

[43]  N. Tretyakova,et al.  Peroxynitrite-induced reactions of synthetic oligonucleotides containing 8-oxoguanine. , 1999, Chemical research in toxicology.

[44]  Surjit B. Dixit,et al.  Free Energy Analysis of ProteinDNA Binding: The EcoRI EndonucleaseDNA Complex , 1999 .

[45]  P. Kollman,et al.  Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate−DNA Helices , 1998 .

[46]  S. Harvey,et al.  The flying ice cube: Velocity rescaling in molecular dynamics leads to violation of energy equipartition , 1998, J. Comput. Chem..

[47]  Sheila S. David,et al.  Chemistry of Glycosylases and Endonucleases Involved in Base-Excision Repair. , 1998, Chemical reviews.

[48]  Slobodan V. Jovanovic,et al.  How Easily Oxidizable Is DNA? One-Electron Reduction Potentials of Adenosine and Guanosine Radicals in Aqueous Solution , 1997 .

[49]  A. Ariza-Castolo,et al.  Versatile behavior of 2‐guanidinobenzimidazole nitrogen atoms toward protonation, coordination and methylation , 1997 .

[50]  J. Cadet,et al.  Oxidative damage to DNA: formation, measurement, and biological significance. , 1997, Reviews of physiology, biochemistry and pharmacology.

[51]  R. Weinberg,et al.  How cancer arises. , 1996, Scientific American.

[52]  T. Halgren.  Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 , 1996, J. Comput. Chem..

[53]  M. Sanner,et al.  Reduced surface: an efficient way to compute molecular surfaces. , 1996, Biopolymers.

[54]  B. Epe,et al.  DNA damage profiles induced by oxidizing agents. , 1996, Reviews of physiology, biochemistry and pharmacology.

[55]  T. Darden,et al.  A smooth particle mesh Ewald method , 1995 .

[56]  Peter A. Kollman,et al.  Application of the multimolecule and multiconformational RESP methodology to biopolymers: Charge derivation for DNA, RNA, and proteins , 1995, J. Comput. Chem..

[57]  A. Lane,et al.  Conformational flexibility in DNA duplexes containing single G.G mismatches. , 1995, European journal of biochemistry.

[58]  B. Honig,et al.  Classical electrostatics in biology and chemistry. , 1995, Science.

[59]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[60]  K. Sharp,et al.  Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models , 1994 .

[61]  B Demple,et al.  Repair of oxidative damage to DNA: enzymology and biology. , 1994, Annual review of biochemistry.

[62]  P. Kollman,et al.  A well-behaved electrostatic potential-based method using charge restraints for deriving atomic char , 1993 .

[63]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[64]  T. Lindahl.  Instability and decay of the primary structure of DNA , 1993, Nature.

[65]  J. Miller,et al.  A repair system for 8-oxo-7,8-dihydrodeoxyguanine. , 1992, Biochemistry.

[66]  A. R. Srinivasan,et al.  The nucleic acid database. A comprehensive relational database of three-dimensional structures of nucleic acids. , 1992, Biophysical journal.

[67]  J. Miller,et al.  Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Dizdaroglu.  Chemical determination of free radical-induced damage to DNA. , 1991, Free radical biology & medicine.

[69]  T. Hayden,et al.  Prediction of DNA structure from sequence: A build‐up technique , 1989, Biopolymers.

[70]  R Lavery,et al.  Conformational and helicoidal analysis of 30 PS of molecular dynamics on the d(CGCGAATTCGCG) double helix: "curves", dials and windows. , 1989, Journal of biomolecular structure & dynamics.

[71]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.

[72]  R Lavery,et al.  The definition of generalized helicoidal parameters and of axis curvature for irregular nucleic acids. , 1988, Journal of biomolecular structure & dynamics.

[73]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[74]  W. Hunter,et al.  Molecular structure of the G.A base pair in DNA and its implications for the mechanism of transversion mutations. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[75]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[76]  M. L. Connolly.  Analytical molecular surface calculation , 1983 .

[77]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[78]  R. Goyal,et al.  Electrochemical and enzymic oxidation of biological purines , 1981 .

[79]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[80]  M. Sundaralingam,et al.  Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. , 1972, Journal of the American Chemical Society.

[81]  J. Pople,et al.  Self—Consistent Molecular Orbital Methods. XII. Further Extensions of Gaussian—Type Basis Sets for Use in Molecular Orbital Studies of Organic Molecules , 1972 .

[82]  H. M. Sobell,et al.  The crystal structure of a hydrogen bonded complex of deoxyguanosine and 5-bromodeoxycytidine. , 1965, Acta crystallographica.

[83]  H. M. Sobell,et al.  THE CRYSTAL STRUCTURE OF A HYDROGEN BONDED COMPLEX OF ADENOSINE AND 5-BROMOURIDINE. , 1965, Acta crystallographica.

[84]  Charles Aldis,et al.  On Cancer , 1817, The London medical and physical journal.