LIVIVO - Search results -

Search results

Result 1 - 10 of total 67

Search options

Article ; Online: A method to accurately quantitate intensities of (32)P-DNA bands when multiple bands appear in a single lane of a gel is used to study dNTP insertion opposite a benzo[a]pyrene-dG adduct by Sulfolobus DNA polymerases Dpo4 and Dbh.

Sholder, Gabriel / Loechler, Edward L

2015 Volume 25, Page(s) 97–103

Abstract: Quantitating relative (32)P-band intensity in gels is desired, e.g., to study primer-extension ... a simple skewed-Gaussian curve from an analogous pure, single-component band (e.g., primer alone ... scan/curve containing multiple bands (e.g., generated in a primer-extension reaction); intensity ...

Abstract	Quantitating relative (32)P-band intensity in gels is desired, e.g., to study primer-extension kinetics of DNA polymerases (DNAPs). Following imaging, multiple (32)P-bands are often present in lanes. Though individual bands appear by eye to be simple and well-resolved, scanning reveals they are actually skewed-Gaussian in shape and neighboring bands are overlapping, which complicates quantitation, because slower migrating bands often have considerable contributions from the trailing edges of faster migrating bands. A method is described to accurately quantitate adjacent (32)P-bands, which relies on having a standard: a simple skewed-Gaussian curve from an analogous pure, single-component band (e.g., primer alone). This single-component scan/curve is superimposed on its corresponding band in an experimentally determined scan/curve containing multiple bands (e.g., generated in a primer-extension reaction); intensity exceeding the single-component scan/curve is attributed to other components (e.g., insertion products). Relative areas/intensities are determined via pixel analysis, from which relative molarity of components is computed. Common software is used. Commonly used alternative methods (e.g., drawing boxes around bands) are shown to be less accurate. Our method was used to study kinetics of dNTP primer-extension opposite a benzo[a]pyrene-N(2)-dG-adduct with four DNAPs, including Sulfolobus solfataricus Dpo4 and Sulfolobus acidocaldarius Dbh. Vmax/Km is similar for correct dCTP insertion with Dpo4 and Dbh. Compared to Dpo4, Dbh misinsertion is slower for dATP (∼20-fold), dGTP (∼110-fold) and dTTP (∼6-fold), due to decreases in Vmax. These findings provide support that Dbh is in the same Y-Family DNAP class as eukaryotic DNAP κ and bacterial DNAP IV, which accurately bypass N(2)-dG adducts, as well as establish the scan-method described herein as an accurate method to quantitate relative intensity of overlapping bands in a single lane, whether generated from (32)P-signals or by other means (e.g., staining).
MeSH term(s)	Archaeal Proteins/genetics ; Archaeal Proteins/metabolism ; Benzopyrenes/chemistry ; DNA Adducts/chemistry ; DNA, Archaeal/analysis ; DNA, Archaeal/metabolism ; DNA-Directed DNA Polymerase/genetics ; DNA-Directed DNA Polymerase/metabolism ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/chemistry ; Deoxyribonucleotides/metabolism ; Electrophoresis, Polyacrylamide Gel/methods ; Image Processing, Computer-Assisted/methods ; Phosphorus Radioisotopes ; Scintillation Counting ; Sensitivity and Specificity ; Sulfolobus acidocaldarius/enzymology ; Sulfolobus solfataricus/enzymology
Chemical Substances	Archaeal Proteins ; Benzopyrenes ; DNA Adducts ; DNA, Archaeal ; Deoxyribonucleotides ; Phosphorus Radioisotopes ; benzo(a)pyrene N2-dG adduct ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Deoxyguanosine (G9481N71RO)
Language	English
Publishing date	2015-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2071608-4
ISSN	1568-7856 ; 1568-7864
ISSN (online)	1568-7856
ISSN	1568-7864
DOI	10.1016/j.dnarep.2014.10.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5555: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

Sholder, Gabriel / Creech, Amanda / Loechler, Edward L

DNA repair

2015 Volume 35, Page(s) 144–153

Abstract: To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and ...

Abstract	To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal to the active site) to suppress dATP/dGTP/dTTP misinsertions; collectively these four structural features enhance DNAP IV's dNTP insertion fidelity opposite a BP-N(2)-dG adduct compared to Dpo4.
MeSH term(s)	Archaeal Proteins/metabolism ; Benzo(a)pyrene/toxicity ; Benzopyrenes/chemistry ; Carcinogens, Environmental/chemistry ; Catalytic Domain/genetics ; DNA Polymerase beta/chemistry ; DNA Polymerase beta/genetics ; Deoxyadenine Nucleotides/metabolism ; Deoxycytosine Nucleotides/chemistry ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/chemistry ; Escherichia coli/genetics ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Mutagens/toxicity ; Sulfolobus solfataricus/genetics ; Thymine Nucleotides/metabolism
Chemical Substances	Archaeal Proteins ; Benzopyrenes ; Carcinogens, Environmental ; Deoxyadenine Nucleotides ; Deoxycytosine Nucleotides ; Escherichia coli Proteins ; Mutagens ; Thymine Nucleotides ; benzo(a)pyrene N2-dG adduct ; 2'-deoxycytidine 5'-triphosphate (2056-98-6) ; Benzo(a)pyrene (3417WMA06D) ; DNA Polymerase beta (EC 2.7.7.-) ; Dpo4 protein, E coli (EC 2.7.7.-) ; Deoxyguanosine (G9481N71RO) ; 2'-deoxyadenosine triphosphate (K8KCC8SH6N) ; thymidine 5'-triphosphate (QOP4K539MU)
Language	English
Publishing date	2015-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2071608-4
ISSN	1568-7856 ; 1568-7864
ISSN (online)	1568-7856
ISSN	1568-7864
DOI	10.1016/j.dnarep.2015.09.020
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5555: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: The role of adduct site-specific mutagenesis in understanding how carcinogen-DNA adducts cause mutations: perspective, prospects and problems.

Loechler, E L

Carcinogenesis

1996 Volume 17, Issue 5, Page(s) 895–902

Abstract: Usually, a particular mutagen/carcinogen forms adducts at many sites in DNA, making it impossible to determine which type of adduct causes which mutation and why. Adduct site-specific mutagenesis studies, in which a single adduct is built into a vector, ... ...

Abstract	Usually, a particular mutagen/carcinogen forms adducts at many sites in DNA, making it impossible to determine which type of adduct causes which mutation and why. Adduct site-specific mutagenesis studies, in which a single adduct is built into a vector, can be used to overcome this problem. The adduct can be situated in double-stranded DNA, single-stranded DNA or in a single-stranded gap, and the benefit and concerns associated with each are addressed. An adduct site-specific study is most useful when it is compared to a mutagenesis study with its corresponding mutagen/carcinogen. Mutations induced by a particular mutagen/carcinogen can be influenced by DNA sequence context, mutagen/carcinogen dose (and other changes in conditions), level of SOS induction, cell type and other factors. Thus, it is important to match the conditions of the adduct study versus the mutagen/carcinogen study as closely as possible. DNA sequence context can profoundly affect the quantitative and qualitative pattern of adduct mutagenesis, which is addressed. In vitro studies with DNA polymerases, frameshift mutagenesis and semi-targeted mutagenesis, whereby a mutation is induced near but not at the site of the adduct, are each discussed. Finally, the relationship between structural studies on adducts and mutagenesis is considered.
MeSH term(s)	Base Sequence ; Carcinogens/metabolism ; Carcinogens/toxicity ; DNA Adducts/toxicity ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation
Chemical Substances	Carcinogens ; DNA Adducts
Language	English
Publishing date	1996-05
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/17.5.895
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1558: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Y-Family DNA polymerases may use two different dNTP shapes for insertion: a hypothesis and its implications.

Chandani, Sushil / Loechler, Edward L

Journal of molecular graphics & modelling

2008 Volume 27, Issue 7, Page(s) 759–769

Abstract: ... several classes. One class includes human DNAP kappa and E. coli DNAP IV, and they insert dCTP in the non ...

Abstract	Chemicals and radiation can damage DNA leading to the formation of adducts/lesions, which - if not removed by DNA repair pathways - usually block replicative DNA polymerases (DNAPs). To overcome such potentially lethal blockage, cells have lesion bypass DNAPs, which are often in the Y-Family and include several classes. One class includes human DNAP kappa and E. coli DNAP IV, and they insert dCTP in the non-mutagenic pathway opposite [+ta]-B[a]P-N(2)-dG, which is the major adduct formed by the environmental carcinogen benzo[a]pyrene. Another class includes hDNAP eta and ecDNAP V, and they insert dATP opposite [+ta]-B[a]P-N(2)-dG in the dominant G-->T mutagenic pathway. Herein we develop a hypothesis for why the IV/kappa-class preferentially does cellular dCTP insertion. On the minor groove side of the active site, Y-Family DNAPs have a cleft/hole that can be analyzed based on an analogy to a "chimney." Our models of DNAP IV show a large chimney opening from which the pyrene of [+ta]-B[a]P-N(2)-dG can protrude, which allows canonical adduct-dG:dCTP pairing. In contrast, our models of DNAP V have small chimney openings that forces adduct-dG downward in the active site such that canonical adduct-dG:dCTP pairing is not possible. Based on X-ray structures, sequence alignment and our modeled structures of Y-Family DNAPs, chimney opening size seems primarily controlled by one amino acid ("flue-handle"), which dictates whether nearby amino acids ("flue") plug the chimney or not. Based on this analysis, a correlation is apparent: the flue is closed in V/eta-class DNAPs giving small chimney openings, while the flue is open for the IV/kappa-class giving large chimney openings. Secondarily, a hypothesis is developed for why the V/eta-class might preferentially do cellular dATP insertion opposite [+ta]-B[a]P-N(2)-dG: the small chimney forces adduct-dG lower in the active site, possibly leading to catalysis using a non-canonical dNTP shape that permits syn-adenine:adduct-dG base pairing. In summary, a hypothesize is developed that the pyrene moiety of [+ta]-B[a]P-N(2)-dG protrudes from the large chimney opening of DNAP IV, thus permitting canonical dCTP:adduct-dG pairing, while the small chimney opening of DNAP V forces [+ta]-B[a]P-N(2)-dG lower down in the active site, in which syn-adenine can pair with adduct-dG via a non-canonical dNTP shape.
MeSH term(s)	Amino Acid Sequence ; Benzopyrenes/chemistry ; Benzopyrenes/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; DNA Adducts/metabolism ; DNA Polymerase beta/metabolism ; DNA Repair ; DNA-Directed DNA Polymerase/chemistry ; DNA-Directed DNA Polymerase/metabolism ; Databases, Protein ; Deoxyadenine Nucleotides/metabolism ; Deoxycytosine Nucleotides/metabolism ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/chemistry ; Deoxyguanosine/metabolism ; Deoxyribonucleotides/metabolism ; Escherichia coli Proteins/metabolism ; Glycine ; Humans ; Models, Genetic ; Models, Molecular ; Molecular Conformation ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nucleic Acid Conformation ; Protein Conformation ; Structure-Activity Relationship
Chemical Substances	Benzopyrenes ; DNA Adducts ; Deoxyadenine Nucleotides ; Deoxycytosine Nucleotides ; Deoxyribonucleotides ; Escherichia coli Proteins ; benzo(a)pyrene N2-dG adduct ; 2'-deoxycytidine 5'-triphosphate (2056-98-6) ; UmuC protein, E coli (98059-80-4) ; Dpo4 protein, E coli (EC 2.7.7.-) ; DNA Polymerase beta (EC 2.7.7.7) ; DNA polymerase V, E coli (EC 2.7.7.7) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; POLK protein, human (EC 2.7.7.7) ; Deoxyguanosine (G9481N71RO) ; 2'-deoxyadenosine triphosphate (K8KCC8SH6N) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2008-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1396450-1
ISSN	1873-4243 ; 1093-3263
ISSN (online)	1873-4243
ISSN	1093-3263
DOI	10.1016/j.jmgm.2008.11.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3491: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: How are potent bulky carcinogens able to induce such a diverse array of mutations?

Loechler, E L

Molecular carcinogenesis

1995 Volume 13, Issue 4, Page(s) 213–219

Abstract: ... substitution mutations (e.g., GC-->TA vs. GC-->AT) depending upon its conformation in DNA, which can be ...

Abstract	Mutations induced by activated benzo[a]pyrene ((+)-anti-B[a]PDE) in Escherichia coli are being investigated, by using both random and adduct-site-specific mutagenesis approaches. A working hypothesis was proposed that the major adduct of (+)-anti-B[a]PDE (formed at N2-Gua) is able to induce different base-substitution mutations (e.g., GC-->TA vs. GC-->AT) depending upon its conformation in DNA, which can be influenced by various factors, notably DNA sequence context. Frameshift mutations are also common with (+)-anti-B[a]PDE, and other work suggested that the frameshift and base-substitution mutagenesis pathways are coupled. The simplest hypothesis to rationalize this interrelationship is that a single (+)-anti-B[a]PDE adduct in a single conformation can be bypassed via either a frameshift or a base-substitution pathway. This counterintuitive notion can be reconciled if there are two different kinds of conformations on the pathway to mutagenesis: a class I conformation, which is the initial conformation of a DNA adduct in double-stranded DNA before its encounter with a DNA polymerase, and a class II conformation, which is the conformation that forms at a single-strand/double-strand DNA junction during replication by a DNA polymerase. Thus, GC-->TA and GC-->AT mutations may be induced by different class I conformations, whereas base substitution and frameshift mutations may be induced by the same class I conformation but by different class II conformations. The pathway of mutagenesis would be dictated by the relevant class I and II conformations, which in turn would be controlled by various factors, notably DNA sequence context.
MeSH term(s)	Benzopyrenes/chemistry ; Carcinogens/chemistry ; DNA Adducts ; DNA, Bacterial/chemistry ; Epoxy Compounds ; Escherichia coli ; Guanine/chemistry ; Mutagenesis ; Mutagens/chemistry ; Nucleic Acid Conformation
Chemical Substances	Benzopyrenes ; Carcinogens ; DNA Adducts ; DNA, Bacterial ; Epoxy Compounds ; Mutagens ; Guanine (5Z93L87A1R)
Language	English
Publishing date	1995-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1004029-8
ISSN	1098-2744 ; 0899-1987
ISSN (online)	1098-2744
ISSN	0899-1987
DOI	10.1002/mc.2940130404
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2664: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: A violation of the Swain-Scott principle, and not SN1 versus SN2 reaction mechanisms, explains why carcinogenic alkylating agents can form different proportions of adducts at oxygen versus nitrogen in DNA.

Loechler, E L

Chemical research in toxicology

1994 Volume 7, Issue 3, Page(s) 277–280

MeSH term(s)	Alkylating Agents/chemistry ; Carcinogens/chemistry ; DNA/chemistry ; DNA Damage ; Kinetics ; Models, Chemical ; Nitrogen/chemistry ; Nucleic Acid Conformation ; Oxygen/chemistry
Chemical Substances	Alkylating Agents ; Carcinogens ; DNA (9007-49-2) ; Nitrogen (N762921K75) ; Oxygen (S88TT14065)
Language	English
Publishing date	1994-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/tx00039a001
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2320: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Molecular modeling benzo[a]pyrene N2-dG adducts in the two overlapping active sites of the Y-family DNA polymerase Dpo4.

Chandani, Sushil / Loechler, Edward L

Journal of molecular graphics & modelling

2007 Volume 25, Issue 5, Page(s) 658–670

Abstract: ... of active site 1 (AS1) is similar to all other families of DNAPs (e.g., the shape of the dNTP). Active site 2 ... AS2), however, is non-canonical (e.g., the beta- and gamma-phosphates in AS2 are approximately ...

Abstract	The potent, ubiquitous environmental mutagen/carcinogen benzo[a]pyrene (B[a]P) induces a single major adduct [+ta]-B[a]P-N2-dG, whose bypass in most cases results in either no mutation (dCTP insertion) or a G-->T mutation (dATP insertion). Translesion synthesis (TLS) of [+ta]-B[a]P-N2-dG generally requires DNA polymerases (DNAPs) in the Y-family, which exist in cells to bypass DNA damage caused by chemicals and radiation. A molecular dynamics (MD) study is described with dCTP opposite [+ta]-B[a]P-N2-dG in Dpo4, which is the best studied Y-family DNAP from a structural point of view. Two orientations of B[a]P-N2-dG (BPmi5 and BPmi3) are considered, along with two orientations of the dCTP (AS1 and AS2), as outlined next. Based on NMR studies, the pyrene moiety of B[a]P-N2-dG is in the minor groove, when paired with dC, and can point toward either the base on the 5'-side (BPmi5) or the 3'-side (BPmi3). Based on published X-ray structures, Dpo4 appears to have two partially overlapping active sites. The architecture of active site 1 (AS1) is similar to all other families of DNAPs (e.g., the shape of the dNTP). Active site 2 (AS2), however, is non-canonical (e.g., the beta- and gamma-phosphates in AS2 are approximately where the alpha- and beta-phosphates are in AS1). In the Dpo4 models generated herein, using the BPmi3 orientation the pyrene moiety of [+ta]-B[a]P-N2-dG points toward the duplex region of the DNA, and is accommodated without distortions in AS1, but with distortions in AS2. Considering the BPmi5 orientation, the pyrene moiety points toward the ss-region of DNA in Dpo4, and sits in a hole defined by the fingers and little fingers domain ("chimney"); BPmi5 is accommodated in AS2 without significant distortions, but poorly in AS1. In summary, when dCTP is paired with [+ta]-B[a]P-N2-dG in the two overlapping active sites in Dpo4, the pyrene in the BPmi3 orientation is accommodated better in active site 1 (AS1), while the pyrene in the BPmi5 orientation is accommodated better in AS2. Finally, we discuss why Y-family DNAPs might have two catalytic active sites.
MeSH term(s)	Benzopyrenes/chemistry ; Catalytic Domain ; Computer Graphics ; Computer Simulation ; Crystallography, X-Ray ; DNA Polymerase beta/chemistry ; DNA Polymerase beta/metabolism ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/chemistry ; Escherichia coli/enzymology ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/metabolism ; Models, Molecular ; Molecular Conformation
Chemical Substances	Benzopyrenes ; Escherichia coli Proteins ; benzo(a)pyrene N2-dG adduct ; DNA Polymerase beta (EC 2.7.7.-) ; Dpo4 protein, E coli (EC 2.7.7.-) ; Deoxyguanosine (G9481N71RO)
Language	English
Publishing date	2007-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1396450-1
ISSN	1873-4243 ; 1093-3263
ISSN (online)	1873-4243
ISSN	1093-3263
DOI	10.1016/j.jmgm.2006.05.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3491: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Molecular modeling in mutagenesis and carcinogenesis.

Loechler, E L

Methods in enzymology

1991 Volume 203, Page(s) 458–476

MeSH term(s)	Base Sequence ; Binding Sites ; Carcinogens/pharmacology ; DNA/chemistry ; DNA/drug effects ; DNA/genetics ; DNA Replication ; Kinetics ; Models, Biological ; Models, Genetic ; Models, Molecular ; Molecular Conformation ; Molecular Sequence Data ; Mutagenesis ; Mutagens/pharmacology ; Nucleic Acid Conformation
Chemical Substances	Carcinogens ; Mutagens ; DNA (9007-49-2)
Language	English
Publishing date	1991
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ISSN	0076-6879
ISSN	0076-6879
DOI	10.1016/0076-6879(91)03025-c
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Rotation about the C6-O6 bond in O6-methylguanine: the syn and anti conformers can be of similar energies in duplex DNA as estimated by molecular modeling techniques.

Loechler, E L

Carcinogenesis

1991 Volume 12, Issue 9, Page(s) 1693–1699

Abstract: O6-Methylguanine (O6MeGua) is generally regarded as the most important premutagenic lesion formed from carcinogenic methylating agents, so its structure and mechanism of action have received considerable attention. Two conformations for the methyl group ... ...

Abstract	O6-Methylguanine (O6MeGua) is generally regarded as the most important premutagenic lesion formed from carcinogenic methylating agents, so its structure and mechanism of action have received considerable attention. Two conformations for the methyl group in O6MeGua are possible: in one the methyl group is syn with respect to the N(1)-position of the purine, points into the helix, and disrupts hydrogen bonding potential; in the second the methyl group is anti with respect to the N1-position of the purine, and points into the major groove. Syn-O6MeGua has been observed when paired with thymine in duplex DNA as determined by NMR, while anti-O6MeGua has been observed when paired with thymine in X-ray diffraction studies. Herein, molecular modeling/computational chemistry is used to evaluate this apparent discrepancy. [N6-Methyladenine (N6MeAde) was also studied, because it is isoelectronic with O6MeGua, and because more information is available about its energetics. Syn-N6MeAde is computed to be favored in small molecules; however, the fraction of the anti-conformer is computed to be approximately 7%, which agrees well with experimentally determined values (4-12%). In contrast, the anti conformation for N6MeAde is calculated to be favored in duplex DNA, which is consistent with what has been observed experimentally using both NMR and X-ray diffraction techniques. The agreement between the calculated and experimentally determined results with N6MeAde suggest that the methods are reasonable.] For O6MeGua, a syn/anti ratio of approximately 10(3) is computed for small molecules. In duplex DNA, syn-O6MeGua is computed to be favored, but the anti-conformer is less than approximately 1 kcal/mol higher in energy. Whether syn- or anti-O6MeGua predominates may depend upon sequence context, as well as environmental factors. The comparison between O6MeGua and N6MeAde suggests a rationale for the puzzling observation that O6MeGua appears to be a cytotoxic lesion in eukaryotic, but not prokaryotic, cells.
MeSH term(s)	Base Sequence ; Carcinogens ; DNA/chemistry ; Guanine/analogs & derivatives ; Guanine/chemistry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Heteroduplexes/chemistry ; Stereoisomerism ; X-Ray Diffraction
Chemical Substances	Carcinogens ; Nucleic Acid Heteroduplexes ; Guanine (5Z93L87A1R) ; DNA (9007-49-2) ; O-(6)-methylguanine (9B710FV2AE)
Language	English
Publishing date	1991-09
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/12.9.1693
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1558: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Molecular modeling studies of O2-alkylthymines and O4-alkylthymines in DNA: structures that may be pertinent to the incorporation of the corresponding dAlkTTP into DNA by DNA polymerases in vitro.

Loechler, E L

Mutation research

1990 Volume 233, Issue 1-2, Page(s) 39–44

MeSH term(s)	Alkylation ; Base Sequence ; DNA/chemistry ; DNA/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Thymine/analogs & derivatives ; Thymine/chemistry ; Thymine/metabolism ; Thymine Nucleotides/metabolism
Chemical Substances	Thymine Nucleotides ; 4-ethylthymine (10557-55-8) ; 4-isopropylthymine (132806-16-7) ; 2-ethylthymine (25628-75-5) ; O-4-methylthymine (25902-89-0) ; O-2-methylthymine (25902-91-4) ; DNA (9007-49-2) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; thymidine 5'-triphosphate (QOP4K539MU) ; Thymine (QR26YLT7LT)
Language	English
Publishing date	1990-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	206607-5
ISSN	1873-135X ; 0027-5107 ; 1383-5718 ; 0165-1110 ; 0165-1161 ; 0165-7992 ; 0921-8777 ; 0165-1218 ; 1383-5726 ; 0167-8817 ; 0921-8734 ; 1383-5742
ISSN (online)	1873-135X
ISSN	0027-5107 ; 1383-5718 ; 0165-1110 ; 0165-1161 ; 0165-7992 ; 0921-8777 ; 0165-1218 ; 1383-5726 ; 0167-8817 ; 0921-8734 ; 1383-5742
DOI	10.1016/0027-5107(90)90149-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1316: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito