1ua1

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[[Image:1ua1.gif|left|200px]]<br /><applet load="1ua1" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1ua1.gif|left|200px]]
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caption="1ua1, resolution 2.00&Aring;" />
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'''Structure of aminofluorene adduct paired opposite cytosine at the polymerase active site.'''<br />
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{{Structure
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|PDB= 1ua1 |SIZE=350|CAPTION= <scene name='initialview01'>1ua1</scene>, resolution 2.00&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=AF:2-AMINOFLUORENE'>AF</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''Structure of aminofluorene adduct paired opposite cytosine at the polymerase active site.'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1UA1 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=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=1UA1 OCA].
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1UA1 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UA1 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15385534 15385534]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15385534 15385534]
[[Category: DNA-directed DNA polymerase]]
[[Category: DNA-directed DNA polymerase]]
[[Category: Geobacillus stearothermophilus]]
[[Category: Geobacillus stearothermophilus]]
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[[Category: dna polymerase i; dna replication; klenow fragment; protein-dna complex; aminofluorene; aromatic amine; dna lesion; translation replication]]
[[Category: dna polymerase i; dna replication; klenow fragment; protein-dna complex; aminofluorene; aromatic amine; dna lesion; translation replication]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:22:12 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:29:13 2008''

Revision as of 12:29, 20 March 2008


PDB ID 1ua1

Drag the structure with the mouse to rotate
, resolution 2.00Å
Ligands: and
Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7
Coordinates: save as pdb, mmCIF, xml



Structure of aminofluorene adduct paired opposite cytosine at the polymerase active site.


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.

About this Structure

1UA1 is a Protein complex structure of sequences from Geobacillus stearothermophilus. Full crystallographic information is available from OCA.

Reference

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

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