1rrq: Difference between revisions
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== | ==MutY adenine glycosylase in complex with DNA containing an A:oxoG pair== | ||
<StructureSection load='1rrq' size='340' side='right'caption='[[1rrq]], [[Resolution|resolution]] 2.22Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1rrq]] 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=1RRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RRQ 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]] 2.22Å</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=CA:CALCIUM+ION'>CA</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=1rrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rrq OCA], [https://pdbe.org/1rrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rrq RCSB], [https://www.ebi.ac.uk/pdbsum/1rrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rrq ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MUTY_GEOSE MUTY_GEOSE] Base excision repair (BER) glycosylase that initiates repair of A:oxoG to C:G by removing the inappropriately paired adenine base from the DNA backbone, generating an abasic site product (PubMed:25995449) (PubMed:14961129). 8-oxoguanine (oxoG) is a genotoxic DNA lesion resulting from oxidation of guanine; this residue is misread by replicative DNA polymerases, that insert adenine instead of cytosine opposite the oxidized damaged base. Shows a powerful dicrimination of A versus C, since it does not cleave cytosine in oxoG:C pairs (PubMed:25995449). May also be able to remove adenine from A:G mispairs, although this activity may not be physiologically relevant (PubMed:14961129).<ref>PMID:25995449</ref> <ref>PMID:14961129</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/rr/1rrq_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=1rrq ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base. | The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base. | ||
Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase.,Fromme JC, Banerjee A, Huang SJ, Verdine GL Nature. 2004 Feb 12;427(6975):652-6. PMID:14961129<ref>PMID:14961129</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 1rrq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Geobacillus stearothermophilus]] | [[Category: Geobacillus stearothermophilus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Banerjee | [[Category: Banerjee A]] | ||
[[Category: Fromme | [[Category: Fromme JC]] | ||
[[Category: Huang | [[Category: Huang SJ]] | ||
[[Category: Verdine | [[Category: Verdine GL]] | ||
Latest revision as of 07:04, 13 August 2026
MutY adenine glycosylase in complex with DNA containing an A:oxoG pair
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