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| | <StructureSection load='6q0c' size='340' side='right'caption='[[6q0c]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6q0c' size='340' side='right'caption='[[6q0c]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6q0c]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_12980 Atcc 12980]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3fsp 3fsp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q0C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q0C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6q0c]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3fsp 3fsp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q0C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NR1:(3R,4R)-3-HYDROXY-4-[(PHOSPHONOOXY)METHYL]PYRROLIDINIUM'>NR1</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NR1:(3R,4R)-3-HYDROXY-4-[(PHOSPHONOOXY)METHYL]PYRROLIDINIUM'>NR1</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6u7t|6u7t]]</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=6q0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q0c OCA], [https://pdbe.org/6q0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q0c RCSB], [https://www.ebi.ac.uk/pdbsum/6q0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q0c ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MutY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1422 ATCC 12980])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenine_glycosylase Adenine glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.31 3.2.2.31] </span></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=6q0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q0c OCA], [http://pdbe.org/6q0c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q0c RCSB], [http://www.ebi.ac.uk/pdbsum/6q0c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q0c 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenine glycosylase]] | + | [[Category: Geobacillus stearothermophilus]] |
| - | [[Category: Atcc 12980]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: David, S S]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Horvath, M P]] | + | [[Category: David SS]] |
| - | [[Category: Murray, V L.O Shea]] | + | [[Category: Horvath MP]] |
| - | [[Category: Russelburg, L P]] | + | [[Category: O'Shea Murray VL]] |
| - | [[Category: Dna repair]] | + | [[Category: Russelburg LP]] |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| - | [[Category: Transition state analog]]
| + | |
| 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 adenine glycosylase MutY selectively initiates repair of OG:A lesions and, by comparison, avoids G:A mispairs. The ability to distinguish these closely related substrates relies on the C-terminal domain of MutY which structurally resembles MutT. To understand the mechanism for substrate specificity, we crystallized MutY in complex with DNA containing G across from the high-affinity azaribose transition state analog. Our structure shows that G is accommodated by the OG site and highlights the role of a serine residue in OG versus G discrimination. The functional significance of Ser308 and its neighboring residues was evaluated by mutational analysis, revealing the critical importance of a beta-loop in the C-terminal domain for mutation suppression in cells, and biochemical performance in vitro. This loop comprising residues Phe307, Ser308, and His309 (Geobacillus stearothermophilus sequence positions) is conserved in MutY but absent in MutT and other DNA repair enzymes, and may therefore serve as a MutY-specific target exploitable by chemical biological probes.
Structural basis for finding OG lesions and avoiding undamaged G by the DNA glycosylase MutY.,Russelburg LP, O'Shea Murray VL, Demir M, Knutsen KR, Sehgal SL, Cao S, David SS, Horvath MP ACS Chem Biol. 2019 Dec 12. doi: 10.1021/acschembio.9b00639. PMID:31829624[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
- ↑ Russelburg LP, O'Shea Murray VL, Demir M, Knutsen KR, Sehgal SL, Cao S, David SS, Horvath MP. Structural basis for finding OG lesions and avoiding undamaged G by the DNA glycosylase MutY. ACS Chem Biol. 2019 Dec 12. doi: 10.1021/acschembio.9b00639. PMID:31829624 doi:http://dx.doi.org/10.1021/acschembio.9b00639
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