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| | ==Crystal Structure of MutY bound to its inhibitor DNA== | | ==Crystal Structure of MutY bound to its inhibitor DNA== |
| - | <StructureSection load='3g0q' size='340' side='right' caption='[[3g0q]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='3g0q' size='340' side='right'caption='[[3g0q]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3g0q]] is a 3 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=3G0Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G0Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3g0q]] 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=3G0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3G0Q 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=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]] 2.2Å</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>, <scene name='pdbligand=A5L:9-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE'>A5L</scene></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=A5L:9-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE'>A5L</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3g0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g0q OCA], [https://pdbe.org/3g0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3g0q RCSB], [https://www.ebi.ac.uk/pdbsum/3g0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3g0q ProSAT]</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=3g0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g0q OCA], [http://pdbe.org/3g0q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3g0q RCSB], [http://www.ebi.ac.uk/pdbsum/3g0q PDBsum]</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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g0/3g0q_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g0/3g0q_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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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: Lee, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Verdine, G L]] | + | [[Category: Lee S]] |
| - | [[Category: 8-oxoguanine]] | + | [[Category: Verdine GL]] |
| - | [[Category: Adenine glycosylase]]
| + | |
| - | [[Category: Dna glycosylase]]
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| - | [[Category: Dna repair]]
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| - | [[Category: Glycosidase]]
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| - | [[Category: Helix-hairpin-helix motif]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolase-dna complex]]
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| - | [[Category: Protein-dna complex]]
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| 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]
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
Adenine DNA glycosylase catalyzes the glycolytic removal of adenine from the promutagenic A.oxoG base pair in DNA. The general features of DNA recognition by an adenine DNA glycosylase, Bacillus stearothermophilus MutY, have previously been revealed via the X-ray structure of a catalytically inactive mutant protein bound to an A:oxoG-containing DNA duplex. Although the structure revealed the substrate adenine to be, as expected, extruded from the DNA helix and inserted into an extrahelical active site pocket on the enzyme, the substrate adenine engaged in no direct contacts with active site residues. This feature was paradoxical, because other glycosylases have been observed to engage their substrates primarily through direct contacts. The lack of direct contacts in the case of MutY suggested that either MutY uses a distinctive logic for substrate recognition or that the X-ray structure had captured a noncatalytically competent state in lesion recognition. To gain further insight into this issue, we crystallized wild-type MutY bound to DNA containing a catalytically inactive analog of 2'-deoxyadenosine in which a single 2'-H atom was replaced by fluorine. The structure of this fluorinated lesion-recognition complex (FLRC) reveals the substrate adenine buried more deeply into the active site pocket than in the prior structure and now engaged in multiple direct hydrogen bonding and hydrophobic interactions. This structure appears to capture the catalytically competent state of adenine DNA glycosylases, and it suggests a catalytic mechanism for this class of enzymes, one in which general acid-catalyzed protonation of the nucleobase promotes glycosidic bond cleavage.
Atomic substitution reveals the structural basis for substrate adenine recognition and removal by adenine DNA glycosylase.,Lee S, Verdine GL Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18497-502. Epub 2009 Oct 19. PMID:19841264[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
- ↑ Lee S, Verdine GL. Atomic substitution reveals the structural basis for substrate adenine recognition and removal by adenine DNA glycosylase. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18497-502. Epub 2009 Oct 19. PMID:19841264
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