1rrs: Difference between revisions
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< | ==MutY adenine glycosylase in complex with DNA containing an abasic site== | ||
<StructureSection load='1rrs' size='340' side='right'caption='[[1rrs]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1rrs]] 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=1RRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RRS 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]] 2.4Å</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>, <scene name='pdbligand=HPD:1-HYDROXY-PENTANE-3,4-DIOL-5-PHOSPHATE'>HPD</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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=1rrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rrs OCA], [https://pdbe.org/1rrs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rrs RCSB], [https://www.ebi.ac.uk/pdbsum/1rrs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rrs 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/1rrs_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=1rrs 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. | |||
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 1rrs" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA glycosylase|DNA glycosylase]] | |||
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | |||
*[[IronâÂÂsulfur proteins|IronâÂÂsulfur proteins]] | |||
== 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 09:07, 23 August 2023
MutY adenine glycosylase in complex with DNA containing an abasic siteMutY adenine glycosylase in complex with DNA containing an abasic site
Structural highlights
FunctionMUTY_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).[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 PubMedThe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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