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New page: left|200px<br /><applet load="1kea" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kea, resolution 2.00Å" /> '''STRUCTURE OF A THERM...
 
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[[Image:1kea.jpg|left|200px]]<br /><applet load="1kea" size="450" color="white" frame="true" align="right" spinBox="true"
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'''STRUCTURE OF A THERMOSTABLE THYMINE-DNA GLYCOSYLASE'''<br />


==Overview==
==STRUCTURE OF A THERMOSTABLE THYMINE-DNA GLYCOSYLASE==
The repair of T:G mismatches in DNA is key for maintaining bacterial, restriction/modification systems and gene silencing in higher eukaryotes., T:G mismatch repair can be initiated by a specific mismatch glycosylase, (MIG) that is homologous to the helix-hairpin-helix (HhH) DNA repair, enzymes. Here, we present a 2.0 A resolution crystal structure and, complementary mutagenesis results for this thermophilic HhH MIG enzyme., The results suggest that MIG distorts the target thymine nucleotide by, twisting the thymine base approximately 90 degrees away from its normal, anti position within DNA. We propose that functionally significant, differences exist in DNA repair enzyme extrahelical nucleotide binding and, catalysis that are characteristic of whether the target base is damaged or, is a normal base within a mispair. These results explain why pure HhH DNA, glycosylases and combined glycosylase/AP lyases cannot be interconverted, by simply altering their functional group chemistry, and how, broad-specificity DNA glycosylase enzymes may weaken the glycosylic, linkage to allow a variety of damaged DNA bases to be excised.
<StructureSection load='1kea' size='340' side='right'caption='[[1kea]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1kea]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KEA 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1kea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kea OCA], [https://pdbe.org/1kea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kea RCSB], [https://www.ebi.ac.uk/pdbsum/1kea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kea ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MIG_METTF MIG_METTF] DNA glycosylase that excises thymine from T/G mismatches and uracil from U/G mismatches (PubMed:11788726, PubMed:8895589). Acts as a repair enzyme able to counteract the mutagenic effect of spontaneous hydrolytic deamination of DNA 5-methylcytosine (5-meC) residues that leads to the formation of T/G mismatches (PubMed:8895589). May also repair U/G mismatches arising from hydrolytic deamination of DNA cytosine residues (PubMed:8895589). G/G, A/G, T/C and U/C are minor substrates (PubMed:11788726, PubMed:8895589).<ref>PMID:11788726</ref> <ref>PMID:8895589</ref>
== 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/ke/1kea_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1kea ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The repair of T:G mismatches in DNA is key for maintaining bacterial restriction/modification systems and gene silencing in higher eukaryotes. T:G mismatch repair can be initiated by a specific mismatch glycosylase (MIG) that is homologous to the helix-hairpin-helix (HhH) DNA repair enzymes. Here, we present a 2.0 A resolution crystal structure and complementary mutagenesis results for this thermophilic HhH MIG enzyme. The results suggest that MIG distorts the target thymine nucleotide by twisting the thymine base approximately 90 degrees away from its normal anti position within DNA. We propose that functionally significant differences exist in DNA repair enzyme extrahelical nucleotide binding and catalysis that are characteristic of whether the target base is damaged or is a normal base within a mispair. These results explain why pure HhH DNA glycosylases and combined glycosylase/AP lyases cannot be interconverted by simply altering their functional group chemistry, and how broad-specificity DNA glycosylase enzymes may weaken the glycosylic linkage to allow a variety of damaged DNA bases to be excised.


==About this Structure==
Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases.,Mol CD, Arvai AS, Begley TJ, Cunningham RP, Tainer JA J Mol Biol. 2002 Jan 18;315(3):373-84. PMID:11786018<ref>PMID:11786018</ref>
1KEA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanothermobacter_thermautotrophicus Methanothermobacter thermautotrophicus] with ZN, ACT, CL and SF4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KEA OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases., Mol CD, Arvai AS, Begley TJ, Cunningham RP, Tainer JA, J Mol Biol. 2002 Jan 18;315(3):373-84. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11786018 11786018]
</div>
<div class="pdbe-citations 1kea" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Methanothermobacter thermautotrophicus]]
[[Category: Methanothermobacter thermautotrophicus]]
[[Category: Single protein]]
[[Category: Arvai AS]]
[[Category: Arvai, A.S.]]
[[Category: Begley TJ]]
[[Category: Begley, T.J.]]
[[Category: Cunningham RP]]
[[Category: Cunningham, R.P.]]
[[Category: Mol CD]]
[[Category: Mol, C.D.]]
[[Category: Tainer JA]]
[[Category: Tainer, J.A.]]
[[Category: ACT]]
[[Category: CL]]
[[Category: SF4]]
[[Category: ZN]]
[[Category: base twisting]]
[[Category: dna glycosylase]]
[[Category: dna mismatch]]
[[Category: dna repair]]
[[Category: methylation]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:06:31 2007''

Latest revision as of 06:23, 13 August 2026

STRUCTURE OF A THERMOSTABLE THYMINE-DNA GLYCOSYLASE

1kea, resolution 2.00Å

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