1kea: Difference between revisions

Latest revision as of 06:23, 13 August 2026

STRUCTURE OF A THERMOSTABLE THYMINE-DNA GLYCOSYLASE

Structural highlights

1kea is a 1 chain structure with sequence from Methanothermobacter thermautotrophicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	ACT, CL, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fondufe-Mittendorf YN, Härer C, Kramer W, Fritz HJ. Two amino acid replacements change the substrate preference of DNA mismatch glycosylase Mig.MthI from T/G to A/G. Nucleic Acids Res. 2002 Jan 15;30(2):614-21. PMID:11788726 doi:10.1093/nar/30.2.614
↑ Horst JP, Fritz HJ. Counteracting the mutagenic effect of hydrolytic deamination of DNA 5-methylcytosine residues at high temperature: DNA mismatch N-glycosylase Mig.Mth of the thermophilic archaeon Methanobacterium thermoautotrophicum THF. EMBO J. 1996 Oct 1;15(19):5459-69 PMID:8895589
↑ Mol CD, Arvai AS, Begley TJ, Cunningham RP, Tainer JA. Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases. J Mol Biol. 2002 Jan 18;315(3):373-84. PMID:11786018 doi:10.1006/jmbi.2001.5264

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Fondufe-Mittendorf YN, Härer C, Kramer W, Fritz HJ. Two amino acid replacements change the substrate preference of DNA mismatch glycosylase Mig.MthI from T/G to A/G. Nucleic Acids Res. 2002 Jan 15;30(2):614-21. PMID:11788726 doi:10.1093/nar/30.2.614

[2] Horst JP, Fritz HJ. Counteracting the mutagenic effect of hydrolytic deamination of DNA 5-methylcytosine residues at high temperature: DNA mismatch N-glycosylase Mig.Mth of the thermophilic archaeon Methanobacterium thermoautotrophicum THF. EMBO J. 1996 Oct 1;15(19):5459-69 PMID:8895589

[3] Mol CD, Arvai AS, Begley TJ, Cunningham RP, Tainer JA. Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases. J Mol Biol. 2002 Jan 18;315(3):373-84. PMID:11786018 doi:10.1006/jmbi.2001.5264

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <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/"methanobacterium_thermoautotrophicus"_(sic)_zeikus_and_wolfe_1972 "methanobacterium thermoautotrophicus" (sic) zeikus and wolfe 1972]. 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>
+<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='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=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</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/GTMR_METTF GTMR_METTF]] Could act in DNA repair. Restriction methylase M.mthtI, which is encoded by this plasmid, generates 5-methylcytosine which is, especially under thermophilic conditions, subject to deamination resulting in G-T mismatches. This protein could correct these mismatches.
+[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]]
@@ Line 14: / Line 15: @@
    <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/initialview01.spt</scriptWhenUnchecked>
+     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Arvai, A S]]
+[[Category: Methanothermobacter thermautotrophicus]]
-[[Category: Begley, T J]]
+[[Category: Arvai AS]]
-[[Category: Cunningham, R P]]
+[[Category: Begley TJ]]
-[[Category: Mol, C D]]
+[[Category: Cunningham RP]]
-[[Category: Tainer, J A]]
+[[Category: Mol CD]]
-[[Category: Base twisting]]
+[[Category: Tainer JA]]
-[[Category: Dna glycosylase]]
-[[Category: Dna mismatch]]
-[[Category: Dna repair]]
-[[Category: Hydrolase]]
-[[Category: Methylation]]

1kea: Difference between revisions

Latest revision as of 06:23, 13 August 2026

STRUCTURE OF A THERMOSTABLE THYMINE-DNA GLYCOSYLASE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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