1ax7
From Proteopedia
(New page: 200px<br /><applet load="1ax7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ax7" /> '''SOLUTION STRUCTURE OF THE [AF]-C8-DG ADDUCT ...) |
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'''SOLUTION STRUCTURE OF THE [AF]-C8-DG ADDUCT POSITIONED AT A TEMPLATE-PRIMER JUNCTION, NMR, 6 STRUCTURES'''<br /> | '''SOLUTION STRUCTURE OF THE [AF]-C8-DG ADDUCT POSITIONED AT A TEMPLATE-PRIMER JUNCTION, NMR, 6 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A solution structural study has been undertaken on the aminofluorene-C8-dG | + | A solution structural study has been undertaken on the aminofluorene-C8-dG ([AF]dG) adduct located at a single strand-double strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13).d (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer junction (designated [AF]dG 13/9-mer) using proton-proton distance and intensity restraints derived from NMR data in combination with a computational protocol, which includes intensity refinement. This single strand-double strand junction models one arm of a replication fork composed of a 13-mer template strand, which contains the [AF]dG modification site, and a 9-mer primer strand, which has been elongated up to, but not including, the modified guanine. The NMR data establish that the duplex segment retains a minimally perturbed B-DNA conformation including Watson-Crick hydrogen-bonding at the junctional dC5.dG22 base pair. The NMR spectra are consistent with the guanine ring of the [AF]dG4 adduct adopting a syn glycosidic torsion angle and being displaced into the major groove with the adjacent dC3 residue displaced into the minor groove. Such a base displacement of the modified guanine is accompanied by stacking of one face of the fluorene ring of [AF]dG4 with the dC5.dG22 base pair, while the other face of the flourene ring is stacked with the purine ring of the nonadjacent dA2 residue in the intensity-refined solution structures of the [AF]dG 13/9-mer. A comparison of structural features of the C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[BP]dG adduct [Cosman et al. (1995) Biochemistry 34, 15334-15350] in the same 13/9-mer junctional sequence context has identified common features associated with the alignment of the modified guanine adducts at the template-primer junction. Thus, despite differences in the covalent linkage site for the C8-[AF]dG and (+)-trans-anti-N2-[BP]dG adducts, one face of the aromatic ring of the carcinogen stacks over the junctional base pair and in so doing displaces the modified guanine in a syn alignment into the major groove. These results lend credence to earlier proposals that such an adduct alignment may represent a common mutagenic conformer at a template-primer junction associated with a replication fork. |
==About this Structure== | ==About this Structure== | ||
| - | 1AX7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with AF as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1AX7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=AF:'>AF</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AX7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Broyde, S.]] | [[Category: Broyde, S.]] | ||
| - | [[Category: Gorin, A | + | [[Category: Gorin, A A.]] |
[[Category: Gu, Z.]] | [[Category: Gu, Z.]] | ||
| - | [[Category: Hingerty, B | + | [[Category: Hingerty, B E.]] |
[[Category: Mao, B.]] | [[Category: Mao, B.]] | ||
| - | [[Category: Patel, D | + | [[Category: Patel, D J.]] |
[[Category: AF]] | [[Category: AF]] | ||
[[Category: aminofluorene adduct]] | [[Category: aminofluorene adduct]] | ||
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[[Category: template-primer junction]] | [[Category: template-primer junction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:49:09 2008'' |
Revision as of 09:49, 21 February 2008
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SOLUTION STRUCTURE OF THE [AF]-C8-DG ADDUCT POSITIONED AT A TEMPLATE-PRIMER JUNCTION, NMR, 6 STRUCTURES
Overview
A solution structural study has been undertaken on the aminofluorene-C8-dG ([AF]dG) adduct located at a single strand-double strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13).d (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer junction (designated [AF]dG 13/9-mer) using proton-proton distance and intensity restraints derived from NMR data in combination with a computational protocol, which includes intensity refinement. This single strand-double strand junction models one arm of a replication fork composed of a 13-mer template strand, which contains the [AF]dG modification site, and a 9-mer primer strand, which has been elongated up to, but not including, the modified guanine. The NMR data establish that the duplex segment retains a minimally perturbed B-DNA conformation including Watson-Crick hydrogen-bonding at the junctional dC5.dG22 base pair. The NMR spectra are consistent with the guanine ring of the [AF]dG4 adduct adopting a syn glycosidic torsion angle and being displaced into the major groove with the adjacent dC3 residue displaced into the minor groove. Such a base displacement of the modified guanine is accompanied by stacking of one face of the fluorene ring of [AF]dG4 with the dC5.dG22 base pair, while the other face of the flourene ring is stacked with the purine ring of the nonadjacent dA2 residue in the intensity-refined solution structures of the [AF]dG 13/9-mer. A comparison of structural features of the C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[BP]dG adduct [Cosman et al. (1995) Biochemistry 34, 15334-15350] in the same 13/9-mer junctional sequence context has identified common features associated with the alignment of the modified guanine adducts at the template-primer junction. Thus, despite differences in the covalent linkage site for the C8-[AF]dG and (+)-trans-anti-N2-[BP]dG adducts, one face of the aromatic ring of the carcinogen stacks over the junctional base pair and in so doing displaces the modified guanine in a syn alignment into the major groove. These results lend credence to earlier proposals that such an adduct alignment may represent a common mutagenic conformer at a template-primer junction associated with a replication fork.
About this Structure
1AX7 is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction., Mao B, Gu Z, Gorin A, Hingerty BE, Broyde S, Patel DJ, Biochemistry. 1997 Nov 25;36(47):14491-501. PMID:9398168
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