1u4b: Difference between revisions
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New page: left|200px<br /><applet load="1u4b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u4b, resolution 1.60Å" /> '''Extension of an aden... |
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== | ==Extension of an adenine-8oxoguanine mismatch== | ||
Aerobic respiration generates reactive oxygen species that can damage | <StructureSection load='1u4b' size='340' side='right'caption='[[1u4b]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1u4b]] 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=1U4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U4B 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</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> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u4b OCA], [https://pdbe.org/1u4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u4b RCSB], [https://www.ebi.ac.uk/pdbsum/1u4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u4b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DPO1_GEOSE DPO1_GEOSE] In addition to polymerase activity, this DNA polymerase exhibits 5' to 3' exonuclease activity. | |||
== 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/u4/1u4b_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=1u4b ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aerobic respiration generates reactive oxygen species that can damage guanine residues and lead to the production of 8-oxoguanine (8oxoG), the major mutagenic oxidative lesion in the genome. Oxidative damage is implicated in ageing and cancer, and its prevalence presents a constant challenge to DNA polymerases that ensure accurate transmission of genomic information. When these polymerases encounter 8oxoG, they frequently catalyse misincorporation of adenine in preference to accurate incorporation of cytosine. This results in the propagation of G to T transversions, which are commonly observed somatic mutations associated with human cancers. Here, we present sequential snapshots of a high-fidelity DNA polymerase during both accurate and mutagenic replication of 8oxoG. Comparison of these crystal structures reveals that 8oxoG induces an inversion of the mismatch recognition mechanisms that normally proofread DNA, such that the 8oxoG.adenine mismatch mimics a cognate base pair whereas the 8oxoG.cytosine base pair behaves as a mismatch. These studies reveal a fundamental mechanism of error-prone replication and show how 8oxoG, and DNA lesions in general, can form mismatches that evade polymerase error-detection mechanisms, potentially leading to the stable incorporation of lethal mutations. | |||
Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase.,Hsu GW, Ober M, Carell T, Beese LS Nature. 2004 Sep 9;431(7005):217-21. Epub 2004 Aug 22. PMID:15322558<ref>PMID:15322558</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 1u4b" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Geobacillus stearothermophilus]] | [[Category: Geobacillus stearothermophilus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Beese | [[Category: Beese LS]] | ||
[[Category: Carell | [[Category: Carell T]] | ||
[[Category: Hsu | [[Category: Hsu GW]] | ||
[[Category: Ober | [[Category: Ober M]] | ||
Latest revision as of 06:38, 23 August 2023
Extension of an adenine-8oxoguanine mismatch
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