1ua0: Difference between revisions

Revision as of 16:22, 21 February 2008

Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase

OverviewOverview

Aromatic amines have been studied for more than a half-century as model carcinogens representing a class of chemicals that form bulky adducts to the C8 position of guanine in DNA. Among these guanine adducts, the N-(2'-deoxyguanosin-8-yl)-aminofluorene (G-AF) and N-2-(2'-deoxyguanosin-8-yl)-acetylaminofluorene (G-AAF) derivatives are the best studied. Although G-AF and G-AAF differ by only an acetyl group, they exert different effects on DNA replication by replicative and high-fidelity DNA polymerases. Translesion synthesis of G-AF is achieved with high-fidelity polymerases, whereas replication of G-AAF requires specialized bypass polymerases. Here we have presented structures of G-AF as it undergoes one round of accurate replication by a high-fidelity DNA polymerase. Nucleotide incorporation opposite G-AF is achieved in solution and in the crystal, revealing how the polymerase accommodates and replicates past G-AF, but not G-AAF. Like an unmodified guanine, G-AF adopts a conformation that allows it to form Watson-Crick hydrogen bonds with an opposing cytosine that results in protrusion of the bulky fluorene moiety into the major groove. Although incorporation opposite G-AF is observed, the C:G-AF base pair induces distortions to the polymerase active site that slow translesion synthesis.

About this StructureAbout this Structure

1UA0 is a Protein complex structure of sequences from Geobacillus stearothermophilus with , and as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.

ReferenceReference

Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase., Hsu GW, Kiefer JR, Burnouf D, Becherel OJ, Fuchs RP, Beese LS, J Biol Chem. 2004 Nov 26;279(48):50280-5. Epub 2004 Sep 22. PMID:15385534

Page seeded by OCA on Thu Feb 21 15:22:11 2008

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OCA

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-[[Image:1ua0.gif|left|200px]]<br /><applet load="1ua0" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1ua0, resolution 2.10&Aring;" />
 '''Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase'''<br />
 ==Overview==
-Aromatic amines have been studied for more than a half-century as model, carcinogens representing a class of chemicals that form bulky adducts to, the C8 position of guanine in DNA. Among these guanine adducts, the, N-(2'-deoxyguanosin-8-yl)-aminofluorene (G-AF) and, N-2-(2'-deoxyguanosin-8-yl)-acetylaminofluorene (G-AAF) derivatives are, the best studied. Although G-AF and G-AAF differ by only an acetyl group, they exert different effects on DNA replication by replicative and, high-fidelity DNA polymerases. Translesion synthesis of G-AF is achieved, with high-fidelity polymerases, whereas replication of G-AAF requires, specialized bypass polymerases. Here we have presented structures of G-AF, as it undergoes one round of accurate replication by a high-fidelity DNA, polymerase. Nucleotide incorporation opposite G-AF is achieved in solution, and in the crystal, revealing how the polymerase accommodates and, replicates past G-AF, but not G-AAF. Like an unmodified guanine, G-AF, adopts a conformation that allows it to form Watson-Crick hydrogen bonds, with an opposing cytosine that results in protrusion of the bulky fluorene, moiety into the major groove. Although incorporation opposite G-AF is, observed, the C:G-AF base pair induces distortions to the polymerase, active site that slow translesion synthesis.
+Aromatic amines have been studied for more than a half-century as model carcinogens representing a class of chemicals that form bulky adducts to the C8 position of guanine in DNA. Among these guanine adducts, the N-(2'-deoxyguanosin-8-yl)-aminofluorene (G-AF) and N-2-(2'-deoxyguanosin-8-yl)-acetylaminofluorene (G-AAF) derivatives are the best studied. Although G-AF and G-AAF differ by only an acetyl group, they exert different effects on DNA replication by replicative and high-fidelity DNA polymerases. Translesion synthesis of G-AF is achieved with high-fidelity polymerases, whereas replication of G-AAF requires specialized bypass polymerases. Here we have presented structures of G-AF as it undergoes one round of accurate replication by a high-fidelity DNA polymerase. Nucleotide incorporation opposite G-AF is achieved in solution and in the crystal, revealing how the polymerase accommodates and replicates past G-AF, but not G-AAF. Like an unmodified guanine, G-AF adopts a conformation that allows it to form Watson-Crick hydrogen bonds with an opposing cytosine that results in protrusion of the bulky fluorene moiety into the major groove. Although incorporation opposite G-AF is observed, the C:G-AF base pair induces distortions to the polymerase active site that slow translesion synthesis.
 ==About this Structure==
-UA0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with SUC, SO4 and AF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UA0 OCA].
+UA0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] with <scene name='pdbligand=SUC:'>SUC</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=AF:'>AF</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UA0 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Geobacillus stearothermophilus]]
 [[Category: Protein complex]]
-[[Category: Becherel, O.J.]]
+[[Category: Becherel, O J.]]
-[[Category: Beese, L.S.]]
+[[Category: Beese, L S.]]
-[[Category: Fuchs, R.P.P.]]
+[[Category: Fuchs, R P.P.]]
-[[Category: Hsu, G.W.]]
+[[Category: Hsu, G W.]]
-[[Category: Kiefer, J.R.]]
+[[Category: Kiefer, J R.]]
 [[Category: AF]]
 [[Category: SO4]]
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 [[Category: dna polymerase i; dna replication; klenow fragment; protein-dna complex; aminofluorene; aromatic amine; dna lesion; translation replication]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 03:36:01 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:22:11 2008''