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[[Image:1ua0.gif|left|200px]]
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{{STRUCTURE_1ua0|  PDB=1ua0  |  SCENE=  }}
'''Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase'''


==Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase==
<StructureSection load='1ua0' size='340' side='right'caption='[[1ua0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ua0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UA0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AF:2-AMINOFLUORENE'>AF</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ua0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ua0 OCA], [https://pdbe.org/1ua0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ua0 RCSB], [https://www.ebi.ac.uk/pdbsum/1ua0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ua0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5KWC1_GEOKA Q5KWC1_GEOKA]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ua/1ua0_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ua0 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Overview==
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<ref>PMID:15385534</ref>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UA0 OCA].
</div>
<div class="pdbe-citations 1ua0" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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]
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
[[Category: DNA-directed DNA polymerase]]
== References ==
[[Category: Becherel, O J.]]
<references/>
[[Category: Beese, L S.]]
__TOC__
[[Category: Fuchs, R P.P.]]
</StructureSection>
[[Category: Hsu, G W.]]
[[Category: Geobacillus stearothermophilus]]
[[Category: Kiefer, J R.]]
[[Category: Large Structures]]
[[Category: Aminofluorene]]
[[Category: Becherel OJ]]
[[Category: Aromatic amine]]
[[Category: Beese LS]]
[[Category: Dna lesion]]
[[Category: Fuchs RPP]]
[[Category: Dna polymerase i]]
[[Category: Hsu GW]]
[[Category: Dna replication]]
[[Category: Kiefer JR]]
[[Category: Klenow fragment]]
[[Category: Protein-dna complex]]
[[Category: Translation replication]]
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