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| | ==Crystal structure of human alklyadenine DNA glycosylase in a lower and higher-affinity complex with DNA== | | ==Crystal structure of human alklyadenine DNA glycosylase in a lower and higher-affinity complex with DNA== |
| - | <StructureSection load='3uby' size='340' side='right' caption='[[3uby]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3uby' size='340' side='right'caption='[[3uby]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3uby]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UBY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3uby]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBY FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDC:N3,N4-ETHENO-2-DEOXYCYTIDINE-5-MONOPHOSPHATE'>EDC</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qi5|3qi5]], [[1ewn|1ewn]], [[1f4r|1f4r]], [[1f6o|1f6o]], [[1bnk|1bnk]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDC:N3,N4-ETHENO-2-DEOXYCYTIDINE-5-MONOPHOSPHATE'>EDC</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MPG, AAG, ANPG, MID1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3uby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uby OCA], [https://pdbe.org/3uby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uby RCSB], [https://www.ebi.ac.uk/pdbsum/3uby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uby ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-3-methyladenine_glycosylase_II DNA-3-methyladenine glycosylase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.21 3.2.2.21] </span></td></tr>
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| - | <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=3uby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uby OCA], [http://pdbe.org/3uby PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3uby RCSB], [http://www.ebi.ac.uk/pdbsum/3uby PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3uby ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/3MG_HUMAN 3MG_HUMAN]] Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions. | + | [https://www.uniprot.org/uniprot/3MG_HUMAN 3MG_HUMAN] Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | To efficiently repair DNA, human alkyladenine DNA glycosylase (AAG) must search the million-fold excess of unmodified DNA bases to find a handful of DNA lesions. Such a search can be facilitated by the ability of glycosylases, like AAG, to interact with DNA using two affinities: a lower-affinity interaction in a searching process and a higher-affinity interaction for catalytic repair. Here, we present crystal structures of AAG trapped in two DNA-bound states. The lower-affinity depiction allows us to investigate, for the first time, the conformation of this protein in the absence of a tightly bound DNA adduct. We find that active site residues of AAG involved in binding lesion bases are in a disordered state. Furthermore, two loops that contribute significantly to the positive electrostatic surface of AAG are disordered. Additionally, a higher-affinity state of AAG captured here provides a fortuitous snapshot of how this enzyme interacts with a DNA adduct that resembles a one-base loop.
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| - | Searching for DNA Lesions: Structural Evidence for Lower- and Higher-Affinity DNA Binding Conformations of Human Alkyladenine DNA Glycosylase.,Setser JW, Lingaraju GM, Davis CA, Samson LD, Drennan CL Biochemistry. 2011 Dec 20. PMID:22148158<ref>PMID:22148158</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3uby" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[DNA glycosylase|DNA glycosylase]] | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-3-methyladenine glycosylase II]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Davis, C A]] | + | [[Category: Davis CA]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Drennan CL]] |
| - | [[Category: Lingaraju, G M]] | + | [[Category: Lingaraju GM]] |
| - | [[Category: Samson, L D]] | + | [[Category: Samson LD]] |
| - | [[Category: Setser, J W]] | + | [[Category: Setser JW]] |
| - | [[Category: Aag]]
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| - | [[Category: Alkyladenine dna glycosylase fold]]
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| - | [[Category: Dna binding]]
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| - | [[Category: Dna repair]]
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| - | [[Category: Hydrolase-dna complex]]
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| - | [[Category: Nucleus]]
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