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2hhu

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[[Image:2hhu.gif|left|200px]]
 
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==C:O6-methyl-guanine in the polymerase postinsertion site (-1 basepair position)==
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The line below this paragraph, containing "STRUCTURE_2hhu", creates the "Structure Box" on the page.
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<StructureSection load='2hhu' size='340' side='right'caption='[[2hhu]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2hhu]] 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=2HHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HHU FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</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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{{STRUCTURE_2hhu| PDB=2hhu | SCENE= }}
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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=2hhu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hhu OCA], [https://pdbe.org/2hhu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hhu RCSB], [https://www.ebi.ac.uk/pdbsum/2hhu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hhu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q5KWC1_GEOKA Q5KWC1_GEOKA]
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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/2hhu_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=2hhu ConSurf].
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<div style="clear:both"></div>
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'''C:O6-methyl-guanine in the polymerase postinsertion site (-1 basepair position)'''
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==See Also==
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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==About this Structure==
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2HHU is a [[Single protein]] structure of sequence 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=2HHU OCA].
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==Reference==
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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://www.ncbi.nlm.nih.gov/pubmed/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: 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 Sun May 4 06:18:49 2008''
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Current revision

C:O6-methyl-guanine in the polymerase postinsertion site (-1 basepair position)

PDB ID 2hhu

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