Free energy profiles of base flipping in intercalative polycyclic aromatic hydrocarbon-damaged DNA duplexes: energetic and structural relationships to nucleotide excision repair susceptibility.

Abstract:

:The crystal structure of Rad4/Rad23, the yeast homolog of the human nucleotide excision repair (NER) lesion recognition factor XPC-RAD23B ( Min , J. H. and Pavletich , N. P. ( 2007 ) Nature 449 , 570 - 575 ) reveals that the lesion-partner base is flipped out of the helix and binds to amino acids of the protein. This suggests the hypothesis that the flipping of this partner base must overcome a free energy barrier, which constitutes one element contributing to changes in the thermodynamic properties induced by the DNA damage and sensed by the recognition protein. We explored this hypothesis by computing complete flipping free energy profiles for two lesions derived from the procarcinogenic polycyclic aromatic hydrocarbons (PAHs), dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P), R-trans-anti-DB[a,l]P-N(6)-dA (R-DB[a,l]P-dA) and R-trans-anti-B[a]P-N(6)-dA (R-B[a]P-dA), and the corresponding unmodified duplex. The DB[a,l]P and B[a]P adducts differ in number and organization of their aromatic rings. We integrate these results with prior profiles for the R-trans-anti-DB[a,l]P-dG adduct ( Zheng , H. et al. ( 2010 ) Chem. Res. Toxicol. 23 , 1868 - 1870 ). All adopt conformational themes involving intercalation of the PAH aromatic ring system into the DNA duplex; however, R-DB[a,l]P-dA and R-B[a]P-dA intercalate from the major groove, while R-DB[a,l]P-dG intercalates from the minor groove. These structural differences produce different computed van der Waals stacking interaction energies between the flipping partner base with the lesion aromatic ring system and adjacent bases; we find that the better the stacking, the higher the relative flipping free energy barrier and hence lower flipping probability. The better relative NER susceptibilities correlate with greater ease of flipping in these three differently intercalated lesions. In addition to partner base flipping, the Rad4/Rad23 crystal structure shows that a protein-β-hairpin, BHD3, intrudes from the major groove side between the DNA strands at the lesion site. We present a molecular modeling study for the R-DB[a,l]P-dG lesion in Rad4/Rad23 showing BHD3 β-hairpin intrusion with lesion eviction, and we hypothesize that lesion steric effects play a role in the recognition of intercalated adducts.

journal_name

Chem Res Toxicol

authors

Cai Y,Zheng H,Ding S,Kropachev K,Schwaid AG,Tang Y,Mu H,Wang S,Geacintov NE,Zhang Y,Broyde S

doi

10.1021/tx400156a

subject

Has Abstract

pub_date

2013-07-15 00:00:00

pages

1115-25

issue

7

eissn

0893-228X

issn

1520-5010

journal_volume

26

pub_type

杂志文章
  • Human serum albumin-benzo[a]pyrene anti-diol epoxide adduct structure elucidation by fluorescence line narrowing spectroscopy.

    abstract::Cryogenic (4-10 K) laser-induced vibrationless ground state and vibronic excited state fluorescence emission spectra of the adducts resulting from reaction in vitro of human serum albumin and the carcinogen (+-)-r-7,t-8-dihydroxy-c-9,c-10-epoxy-7,8,9,10- tetrahydrobenzo[a]-pyrene were recorded in order to determine th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00025a012

    authors: Day BW,Doxtader MM,Rich RH,Skipper PL,Singh K,Dasari RR,Tannenbaum SR

    更新日期:1992-01-01 00:00:00

  • DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure.

    abstract::DNA oxidation damage has been regarded as one of the possible mechanisms for the hepatic carcinogenesis of dioxin-like compounds (DLCs). In this study, we evaluated the toxic equivalency factor (TEF) from the standpoint of induced DNA oxidation products and their relationship to toxicity and carcinogenicity. Nine DNA ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.6b00368

    authors: Gao L,Mutlu E,Collins LB,Walker NJ,Hartwell HJ,Olson JR,Sun W,Gold A,Ball LM,Swenberg JA

    更新日期:2017-03-20 00:00:00

  • Endocrine disruption screening by protein and gene expression of vitellogenin in freshly isolated and cryopreserved rainbow trout hepatocytes.

    abstract::Xenobiotics may activate the estrogen receptor, resulting in alteration of normal endocrine functions in animals and humans. Consequently, this necessitates development of assay end points capable of identifying estrogenic xenobiotics. In the present study, we screened the potential estrogenicity of chemicals via thei...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx5002089

    authors: Markell LK,Mingoia RT,Peterson HM,Yao J,Waters SM,Finn JP,Nabb DL,Han X

    更新日期:2014-08-18 00:00:00

  • Regioselectivity and quantitative structure-activity relationships for the conjugation of a series of fluoronitrobenzenes by purified glutathione S-transferase enzymes from rat and man.

    abstract::Quantitative structure-activity relationships (QSAR's) are described for the rate of conjugation of a series of fluoronitrobenzenes with cytosolic as well as with two major alpha and mu class enzymes of rat and human liver, viz., glutathione S-transferases (GST) 1-1, 3-3, A1-1, and M1a-1a. For all purified enzymes stu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx9501804

    authors: Soffers AE,Ploemen JH,Moonen MJ,Wobbes T,van Ommen B,Vervoort J,van Bladeren PJ,Rietjens IM

    更新日期:1996-04-01 00:00:00

  • A study of inactivation reactions of N-acetylcysteine with mucochloric acid, a mutagenic product of the chlorination of humic substances in water.

    abstract::The Salmonella typhimurium (TA100) mutagenic compound, mucochloric acid [3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA)], was inactivated by in vitro N-acetylcysteine (NAC). The reaction of MCA with NAC at pH7 was second order and gave products 4, 5, and 6a that resulted from the displacement of chlorine from C-3 or C-4 ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00029a005

    authors: LaLonde RT,Xie S

    更新日期:1992-09-01 00:00:00

  • Mechanism of reaction of beta-(aryloxy)acroleins with nucleosides.

    abstract::The mechanism of DNA adduct formation by acroleins substituted with good leaving groups in the beta-position was investigated using [3-2H]-3-(p-nitrophenoxy)acrolein (1). Reaction of 1 with guanosine at acidic pH produced 9-beta-D-ribofuranosylpyrimido[1,2-alpha]purin-10(3H)-one containing equal amounts of deuterium a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx950105t

    authors: Reddy GR,Marnett LJ

    更新日期:1996-01-01 00:00:00

  • Quantitation of pyridyloxobutyl DNA adducts of tobacco-specific nitrosamines in rat tissue DNA by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

    abstract::The tobacco-specific nitrosamines N'-nitrosonornicotine (NNN, 1) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 2) are potent carcinogens in rodents. Bioactivation of NNN and NNK by cytochrome P450 enzymes generates a pyridyloxobutylating agent 6, which alkylates DNA to produce pyridyloxobutyl (POB)-DNA addu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx050351x

    authors: Lao Y,Villalta PW,Sturla SJ,Wang M,Hecht SS

    更新日期:2006-05-01 00:00:00

  • Identification and quantification of DNA adducts in the oral tissues of mice treated with the environmental carcinogen dibenzo[a,l]pyrene by HPLC-MS/MS.

    abstract::Tobacco smoking is one of the leading causes for oral cancer. Dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and a tobacco smoke constituent, is the most carcinogenic polycyclic aromatic hydrocarbon (PAH) tested to date in several animal models (target organs: skin, lung, ovary, and mammary tissues). We hav...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200188j

    authors: Zhang SM,Chen KM,Aliaga C,Sun YW,Lin JM,Sharma AK,Amin S,El-Bayoumy K

    更新日期:2011-08-15 00:00:00

  • Identification of individual benzo[c]phenanthrene dihydrodiol epoxide-DNA adducts by the 32P-postlabeling assay.

    abstract::Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separat...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00029a015

    authors: Canella KA,Peltonen K,Yagi H,Jerina DM,Dipple A

    更新日期:1992-09-01 00:00:00

  • In vitro flavon-3-ol oxidation mediated by a B ring hydroxylation pattern.

    abstract::Flavonols are potent naturally occurring antioxidants. Chemical oxidation reactions in combination with modern spectroscopic techniques have been employed to identify oxidized flavonoid products. Although many oxidized derivatives have been generated from commercially available starting materials, few studies have dev...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx034242z

    authors: Krishnamachari V,Levine LH,Zhou C,Paré PW

    更新日期:2004-06-01 00:00:00

  • In vitro model of mammary estrogen metabolism: structural and kinetic differences between catechol estrogens 2- and 4-hydroxyestradiol.

    abstract::Estrogens and their oxidative metabolites, the catechol estrogens, have been implicated in the development of breast cancer; yet, relatively little is known about estrogen metabolism in the breast. To determine how the parent hormone, 17 beta-estradiol (E(2)), is metabolized, we used recombinant, purified phase I enzy...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx0498657

    authors: Dawling S,Hachey DL,Roodi N,Parl FF

    更新日期:2004-09-01 00:00:00

  • Chemical and glutathione conjugation-related degradation of fotemustine: formation and characterization of a glutathione conjugate of diethyl (1-isocyanatoethyl)phosphonate, a reactive metabolite of fotemustine.

    abstract::Fotemustine is a chemotherapeutic drug for the treatment of melanoma. In this study, we investigated the metabolic and chemical stability of fotemustine with 31P-NMR and FAB-MS. In the absence of GSH, 95% of fotemustine decomposed rapidly into a reactive diethyl ethylphosphonate (DEP) isocyanate, both in rat liver S9 ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00039a016

    authors: Brakenhoff JP,Commandeur JN,de Kanter FJ,van Baar BL,Luijten WC,Vermeulen NP

    更新日期:1994-05-01 00:00:00

  • Tobacco-specific nitrosamine-derived O2-alkylthymidines are potent mutagenic lesions in SOS-induced Escherichia coli.

    abstract::To investigate the biological effects of the O(2)-alkylthymidines induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), we have replicated a plasmid containing O(2)-methylthymidine (O(2)-Me-dT) or O(2)-[4-(3-pyridyl-4-oxobut-1-yl]thymidine (O(2)-POB-dT) in Escherichia coli w...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200435d

    authors: Jasti VP,Spratt TE,Basu AK

    更新日期:2011-11-21 00:00:00

  • Rapid screening of glutathione-trapped reactive metabolites by linear ion trap mass spectrometry with isotope pattern-dependent scanning and postacquisition data mining.

    abstract::The present study describes a novel integrated approach for rapid analysis of reactive metabolites with a linear ion trap mass spectrometer (LTQ). In this approach, an isotope pattern-dependent scanning method was applied to the data acquisition of glutathione (GSH)-trapped reactive metabolites. Recorded full-scan MS ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx8001115

    authors: Ma L,Wen B,Ruan Q,Zhu M

    更新日期:2008-07-01 00:00:00

  • Serum metabolomics reveals irreversible inhibition of fatty acid beta-oxidation through the suppression of PPARalpha activation as a contributing mechanism of acetaminophen-induced hepatotoxicity.

    abstract::Metabolic bioactivation, glutathione depletion, and covalent binding are the early hallmark events after acetaminophen (APAP) overdose. However, the subsequent metabolic consequences contributing to APAP-induced hepatic necrosis and apoptosis have not been fully elucidated. In this study, serum metabolomes of control ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx800464q

    authors: Chen C,Krausz KW,Shah YM,Idle JR,Gonzalez FJ

    更新日期:2009-04-01 00:00:00

  • Hypochlorous acid-mediated oxidation of lipid components and antioxidants present in low-density lipoproteins: absolute rate constants, product analysis, and computational modeling.

    abstract::Oxidation of low-density lipoproteins (LDL) is believed to contribute to the increased uptake of LDL by macrophages, which is an early event in atherosclerosis. Hypochlorous acid (HOCl) has been implicated as one of the major oxidants involved in these processes. In a previous study, the rates of reaction of HOCl with...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx025670s

    authors: Pattison DI,Hawkins CL,Davies MJ

    更新日期:2003-04-01 00:00:00

  • Urine metabolites reflect time-dependent effects of cyclosporine and sirolimus on rat kidney function.

    abstract::The clinical use of the immunosuppressant calcineurin inhibitor cyclosporine is limited by its nephrotoxicity. This is enhanced when combined with the immunosuppressive mTOR inhibitor sirolimus. Nephrotoxicity of both drugs is not yet fully understood. The goal was to gain more detailed mechanistic insights into the t...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx800253x

    authors: Klawitter J,Bendrick-Peart J,Rudolph B,Beckey V,Klawitter J,Haschke M,Rivard C,Chan L,Leibfritz D,Christians U,Schmitz V

    更新日期:2009-01-01 00:00:00

  • Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing Supplements.

    abstract::Docosahexaenoic acid (DHA) is a semiessential polyunsaturated fatty acid (PUFA) for eukaryotic cells that is found in natural sources such as fish and algal oils and widely used as an ingredient for omega-3 containing foods or supplements. DHA effects are connected to its natural structure with six cis double bonds, b...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.8b00021

    authors: Menounou G,Giacometti G,Scanferlato R,Dambruoso P,Sansone A,Tueros I,Amézaga J,Chatgilialoglu C,Ferreri C

    更新日期:2018-03-19 00:00:00

  • Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity.

    abstract::N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N7, guanine O6, and adenine N3. Dixit and Gold [(1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8039-8043] reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU i...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00015a002

    authors: Lord HL,Josephy PD,Snieckus VA

    更新日期:1990-05-01 00:00:00

  • Assessment of Single-Photon Ionization Mass Spectrometry for Online Monitoring of in Vitro Aerosol Exposure Experiments.

    abstract::Chemical and physical characterization of transported evolving aerosols in an in vitro system is complex. The challenges include appropriate sampling sensitivity, measurement capabilities, and performing online measurements of constituents in the flowing aerosol during exposure. We assessed the performance of single-p...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00381

    authors: Frege C,Asgari M,Steiner S,Ferreira S,Majeed S,Lucci F,Frentzel S,Hoeng J,Kuczaj AK

    更新日期:2020-02-17 00:00:00

  • Quantitation of 7-ethylguanine in leukocyte DNA from smokers and nonsmokers by liquid chromatography-nanoelectrospray-high resolution tandem mass spectrometry.

    abstract::There is considerable evidence for the exposure of humans to an unknown ethylating agent, and some studies indicate that cigarette smoking may be one source of this exposure. Therefore, we have developed a liquid chromatography-nanoelectrospray-high resolution tandem mass spectrometry-selected reaction monitoring (LC-...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200262d

    authors: Balbo S,Villalta PW,Hecht SS

    更新日期:2011-10-17 00:00:00

  • Ring addition of the alpha-amino group of glutathione increases the reactivity of benzoquinone thioethers.

    abstract::2-(Glutathion-S-yl)-1,4-benzoquinone was found to be remarkably unstable in phosphate buffer (pH 7.4) even in the absence of oxygen. Intramolecular addition of the alpha-amino group of the glutamate residue to the quinone ring yielded ultimately 2,3-(glutathion-N, S-yl)-1,4-benzoquinone and 2,6-(glutathion-N,S-yl)-1,4...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx9800699

    authors: Alt C,Eyer P

    更新日期:1998-10-01 00:00:00

  • Allergic contact dermatitis--formation, structural requirements, and reactivity of skin sensitizers.

    abstract::Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章,评审

    doi:10.1021/tx7002239

    authors: Karlberg AT,Bergström MA,Börje A,Luthman K,Nilsson JL

    更新日期:2008-01-01 00:00:00

  • Mechanistic Insights into the Cytotoxicity of Graphene Oxide Derivatives in Mammalian Cells.

    abstract::Graphene oxide derivatives (GODs) have superb physical/chemical properties with promise for applications in biomedicine. Shape, size, and chemistry of the GODs are identified as the key parameters that impact any biological system. In this work, the GODs with a wide range of shapes (sheets, helical/longitudinal ribbon...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00391

    authors: Lu P,Zehtab Yazdi A,Han XX,Al Husaini K,Haime J,Waye N,Chen P

    更新日期:2020-09-21 00:00:00

  • Oxidative bioactivation of abacavir in subcellular fractions of human antigen presenting cells.

    abstract::Human exposure to abacavir, a primary alcohol antiretroviral, is associated with the development of immunological drug reactions in individuals carrying the HLA risk allele B*57:01. Interaction of abacavir with antigen presenting cells results in cell activation through an Hsp70-mediated Toll-like receptor pathway and...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx400041v

    authors: Bell CC,Santoyo Castelazo A,Yang EL,Maggs JL,Jenkins RE,Tugwood J,O'Neill PM,Naisbitt DJ,Park BK

    更新日期:2013-07-15 00:00:00

  • Chemical Interaction of Protein Cysteine Residues with Reactive Metabolites of Methyleugenol.

    abstract::Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced to...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.6b00290

    authors: Feng Y,Wang H,Wang Q,Huang W,Peng Y,Zheng J

    更新日期:2017-02-20 00:00:00

  • Estrogen carcinogenesis: specific identification of estrogen-modified nucleobase in breast tissue from women.

    abstract::Prolonged exposure to estrogens correlates with an increased risk for breast cancer. One explanation is that estrogen metabolites cause mutations by reacting with DNA, leading to depurination. We describe an extraction procedure and a liquid chromatographic tandem mass spectrometric (LC/MS/MS) assay to detect estrone-...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx8001737

    authors: Zhang Q,Aft RL,Gross ML

    更新日期:2008-08-01 00:00:00

  • Reactivity with Tris(hydroxymethyl)aminomethane confounds immunodetection of acrolein-adducted proteins.

    abstract::The toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biol...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx0341106

    authors: Burcham PC,Fontaine FR,Petersen DR,Pyke SM

    更新日期:2003-10-01 00:00:00

  • (Carboxyalkyl)pyrroles in human plasma and oxidized low-density lipoproteins.

    abstract::Free-radical oxidation of human plasma low-density lipoprotein (LDL) produces (carboxyalkyl)pyrrole (CAP) epitopes that were detected with enzyme-linked immunosorbent assays using antibodies raised against keyhole limpet hemocyanin (KLH)-bound 2-(omega-carboxyheptyl)-pyrrole (CHP) and 2-(omega-carboxypropyl)pyrrole (C...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx970112c

    authors: Kaur K,Salomon RG,O'Neil J,Hoff HF

    更新日期:1997-12-01 00:00:00

  • Reactive sulfur species: kinetics and mechanism of the hydrolysis of cysteine thiosulfinate ester.

    abstract::The kinetics and mechanisms of the hydrolysis of cysteine thiosulfinate ester (CyS(O)SCy ( x- ), x = 0-2) have been investigated by stopped-flow spectrophotometry between pH 6 and pH 14. The rate-limiting reaction of hydroxide is observed for pH < 13. More complicated kinetics are observed above pH 13, where the hydro...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx700168z

    authors: Nagy P,Ashby MT

    更新日期:2007-09-01 00:00:00