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| | <StructureSection load='4ypr' size='340' side='right'caption='[[4ypr]], [[Resolution|resolution]] 2.59Å' scene=''> | | <StructureSection load='4ypr' size='340' side='right'caption='[[4ypr]], [[Resolution|resolution]] 2.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ypr]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_12980 Atcc 12980]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YPR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ypr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YPR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> | + | </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=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</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=4ypr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypr OCA], [https://pdbe.org/4ypr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ypr RCSB], [https://www.ebi.ac.uk/pdbsum/4ypr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypr ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yoq|4yoq]], [[4yph|4yph]]</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ypr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ypr OCA], [http://pdbe.org/4ypr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ypr RCSB], [http://www.ebi.ac.uk/pdbsum/4ypr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ypr ProSAT]</span></td></tr> | + | |
| | </table> | | </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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[DNA glycosylase|DNA glycosylase]] | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 12980]] | + | [[Category: Geobacillus stearothermophilus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lee, S]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Verdine, G L]] | + | [[Category: Lee S]] |
| - | [[Category: Wang, L]] | + | [[Category: Verdine GL]] |
| - | [[Category: 8-oxoguanine]] | + | [[Category: Wang L]] |
| - | [[Category: Anti-substrate]]
| + | |
| - | [[Category: Base-excision repair]]
| + | |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| Structural highlights
Function
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).[1] [2]
Publication Abstract from PubMed
The highly mutagenic A:oxoG base-pair in DNA most frequently arises by aberrant replication of the primary oxidative lesion C:oxoG. This lesion is particularly insidious, because neither of its constituent nucleobases faithfully transmit genetic information from the original C:G base-pair. Repair of A:oxoG is initiated by adenine DNA glycosylase which catalyzes hydrolytic cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY in bacteria and hMYH in humans, scrupulously avoid processing of C:oxoG, because cleavage of the C residue in C:oxoG would actually promote mutagenic conversion to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY, using a synthetic crystallography approach to capture the enzyme in the process of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only fleetingly. We find that MutY uses two distinct strategies to avoid presentation of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves as a decoy for C, and secondly, repulsive forces with a key active site residue prevent stable insertion of C into the nucleobase-recognition pocket within the enzyme active site.
Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase.,Wang L, Lee SJ, Verdine G J Biol Chem. 2015 May 20. pii: jbc.M115.657866. PMID:25995449[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang L, Lee SJ, Verdine G. Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase. J Biol Chem. 2015 May 20. pii: jbc.M115.657866. PMID:25995449 doi:http://dx.doi.org/10.1074/jbc.M115.657866
- ↑ Fromme JC, Banerjee A, Huang SJ, Verdine GL. Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase. Nature. 2004 Feb 12;427(6975):652-6. PMID:14961129 doi:10.1038/nature02306
- ↑ Wang L, Lee SJ, Verdine G. Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase. J Biol Chem. 2015 May 20. pii: jbc.M115.657866. PMID:25995449 doi:http://dx.doi.org/10.1074/jbc.M115.657866
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