3d4v
From Proteopedia
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| ==Crystal Structure of an AlkA Host/Guest Complex N7MethylGuanine:Cytosine Base Pair== | ==Crystal Structure of an AlkA Host/Guest Complex N7MethylGuanine:Cytosine Base Pair== | ||
| - | <StructureSection load='3d4v' size='340' side='right' caption='[[3d4v]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='3d4v' size='340' side='right'caption='[[3d4v]], [[Resolution|resolution]] 2.90Å' scene=''> | 
| == Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3d4v]] is a 8 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3d4v]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D4V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4V FirstGlance]. <br> | 
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | 
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMG:2-AMINO-9-(2-DEOXY-2-FLUORO-5-O-PHOSPHONO-BETA-D-ARABINOFURANOSYL)-7-METHYL-6-OXO-6,9-DIHYDRO-1H-PURIN-7-IUM'>FMG</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=3d4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4v OCA], [https://pdbe.org/3d4v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4v RCSB], [https://www.ebi.ac.uk/pdbsum/3d4v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4v ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
| </table> | </table> | ||
| == Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/3MG2_ECOLI 3MG2_ECOLI] Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and O2-methylcytosine from the damaged DNA polymer formed by alkylation lesions. | 
| == 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/d4/3d4v_consurf.spt"</scriptWhenChecked> | + |     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/3d4v_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> | ||
| Line 20: | Line 20: | ||
| </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=3d4v ConSurf]. | </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=3d4v ConSurf]. | ||
| <div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The predominant product of aberrant DNA methylation is the genotoxic lesion N7-methyl-2'-deoxyguanosine (m7dG). M7dG is recognized and excised by lesion-specific DNA glycosylases, namely AlkA in E. coli and Aag in humans. Structural studies of m7dG recognition and catalysis by these enzymes have been hampered due to a lack of efficient means by which to incorporate the chemically labile m7dG moiety site-specifically into DNA on a preparative scale. Here we report a solution to this problem. We stabilized the lesion toward acid-catalyzed and glycosylase-catalyzed depurination by 2'-fluorination and toward base-catalyzed degradation using mild, nonaqueous conditions in the DNA deprotection reaction. Duplex DNA containing 2'-fluoro-m7dG (Fm7dG) cocrystallized with AlkA as a host-guest complex in which the lesion-containing segment of DNA was nearly devoid of protein contacts, thus enabling the first direct visualization of the N7-methylguanine lesion nucleobase in DNA. The structure reveals that the base-pairing mode of Fm7dG:C is nearly identical to that of G:C, and Fm7dG does not induce any apparent structural disturbance of the duplex structure. These observations suggest that AlkA and Aag must perform a structurally invasive interrogation of DNA in order to detect the presence of intrahelical m7dG lesions. | ||
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| - | Synthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanine.,Lee S, Bowman BR, Ueno Y, Wang S, Verdine GL J Am Chem Soc. 2008 Sep 3;130(35):11570-1. Epub 2008 Aug 8. PMID:18686953<ref>PMID:18686953</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3d4v" style="background-color:#fffaf0;"></div> | ||
| ==See Also== | ==See Also== | ||
| - | *[[DNA glycosylase|DNA glycosylase]] | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | 
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| __TOC__ | __TOC__ | ||
| </StructureSection> | </StructureSection> | ||
| - | [[Category:  | + | [[Category: Escherichia coli]] | 
| - | [[Category:  | + | [[Category: Large Structures]] | 
| - | [[Category: Bowman | + | [[Category: Bowman BR]] | 
| - | [[Category: Lee | + | [[Category: Lee S]] | 
| - | [[Category: Verdine | + | [[Category: Verdine GL]] | 
| - | [[Category: Wang | + | [[Category: Wang S]] | 
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Current revision
Crystal Structure of an AlkA Host/Guest Complex N7MethylGuanine:Cytosine Base Pair
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