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2hhq

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(New page: 200px<br /><applet load="2hhq" size="350" color="white" frame="true" align="right" spinBox="true" caption="2hhq, resolution 1.800&Aring;" /> '''O6-methyl-guanine:T...)
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[[Image:2hhq.gif|left|200px]]<br /><applet load="2hhq" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2hhq, resolution 1.800&Aring;" />
 
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'''O6-methyl-guanine:T pair in the polymerase-10 basepair position'''<br />
 
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==Overview==
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==O6-methyl-guanine:T pair in the polymerase-10 basepair position==
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Methylating agents are widespread environmental carcinogens that generate, a broad spectrum of DNA damage. Methylation at the guanine O(6) position, confers the greatest mutagenic and carcinogenic potential. DNA polymerases, insert cytosine and thymine with similar efficiency opposite, O(6)-methyl-guanine (O6MeG). We combined pre-steady-state kinetic analysis, and a series of nine x-ray crystal structures to contrast the reaction, pathways of accurate and mutagenic replication of O6MeG in a high-fidelity, DNA polymerase from Bacillus stearothermophilus. Polymerases achieve, substrate specificity by selecting for nucleotides with shape and, hydrogen-bonding patterns that complement a canonical DNA template. Our, structures reveal that both thymine and cytosine O6MeG base pairs evade, proofreading by mimicking the essential molecular features of canonical, substrates. The steric mimicry depends on stabilization of a rare cytosine, tautomer in C.O6MeG-polymerase complexes. An unusual electrostatic, interaction between O-methyl protons and a thymine carbonyl oxygen helps, stabilize T.O6MeG pairs bound to DNA polymerase. Because DNA methylators, constitute an important class of chemotherapeutic agents, the molecular, mechanisms of replication of these DNA lesions are important for our, understanding of both the genesis and treatment of cancer.
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<StructureSection load='2hhq' size='340' side='right'caption='[[2hhq]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2hhq]] 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=2HHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HHQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6OG:6-O-METHYL+GUANOSINE-5-MONOPHOSPHATE'>6OG</scene>, <scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hhq OCA], [https://pdbe.org/2hhq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hhq RCSB], [https://www.ebi.ac.uk/pdbsum/2hhq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hhq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q45458_GEOSE Q45458_GEOSE] In addition to polymerase activity, this DNA polymerase exhibits 5'-3' exonuclease activity.[RuleBase:RU004460]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hh/2hhq_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2hhq ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2HHQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=MG:'>MG</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=2HHQ OCA].
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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The structural basis for the mutagenicity of O(6)-methyl-guanine lesions., Warren JJ, Forsberg LJ, Beese LS, Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19701-6. Epub 2006 Dec 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17179038 17179038]
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[[Category: DNA-directed DNA polymerase]]
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[[Category: Geobacillus stearothermophilus]]
[[Category: Geobacillus stearothermophilus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Beese, L.S.]]
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[[Category: Beese LS]]
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[[Category: Forsberg, L.J.]]
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[[Category: Forsberg LJ]]
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[[Category: Warren, J.J.]]
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[[Category: Warren JJ]]
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[[Category: MG]]
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[[Category: SO4]]
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[[Category: SUC]]
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[[Category: dna polymerase i]]
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[[Category: dna replication]]
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[[Category: klenow fragment]]
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[[Category: o6-methyl-guanine]]
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[[Category: protein-dna complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 20:21:27 2008''
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Current revision

O6-methyl-guanine:T pair in the polymerase-10 basepair position

PDB ID 2hhq

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