4ij0
From Proteopedia
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| ==Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing transition mutation== | ==Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing transition mutation== | ||
| - | <StructureSection load='4ij0' size='340' side='right' caption='[[4ij0]], [[Resolution|resolution]] 1.54Å' scene=''> | + | <StructureSection load='4ij0' size='340' side='right'caption='[[4ij0]], [[Resolution|resolution]] 1.54Å' scene=''> | 
| == Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4ij0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IJ0 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4ij0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IJ0 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]] 1.54Å</td></tr> | 
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C6G:6-(CARBOXYMETHOXY)-9-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)-9H-PURIN-2-AMINE'>C6G</scene>, <scene name='pdbligand=HT:2-(4-HYDROXYPHENYL)-5-(4-METHYL-1-PIPERAZINYL)-2,5-BI-BENZIMIDAZOLE'>HT</scene>, <scene name='pdbligand=SR:STRONTIUM+ION'>SR</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=4ij0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ij0 OCA], [https://pdbe.org/4ij0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ij0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ij0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ij0 ProSAT]</span></td></tr> | 
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
| </table> | </table> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | N-nitrosation of glycine and its derivatives generates potent alkylating agents that can lead to the formation of O6-carboxymethylguanine (O6-CMG) in DNA. O6-CMG has been identified in DNA derived from human colon tissue, and its occurrence has been linked to diets high in red and processed meats. By analogy to O6-methylguanine, O6-CMG is expected to be highly mutagenic, inducing G to A mutations during DNA replication that can increase the risk of gastrointestinal and other cancers. Two crystal structures of DNA dodecamers d(CGCG[O6-CMG]ATTCGCG) and d(CGC[O6-CMG]AATTCGCG) in complex with Hoechst33258 reveal that each can form a self-complementary duplex to retain the B-form conformation. Electron density maps clearly show that O6-CMG forms a Watson-Crick-type pair with thymine similar to the canonical A:T pair, and it forms a reversed wobble pair with cytosine. In situ structural modeling suggests that a DNA polymerase can accept the Watson-Crick-type pair of O6-CMG with thymine, but might also accept the reversed wobble pair of O6-CMG with cytosine. Thus, O6-CMG would permit the mis-incorporation of dTTP during DNA replication. Alternatively, the triphosphate that would be formed by carboxymethylation of the nucleotide triphosphate pool d[O6-CMG]TP might compete with dATP incorporation opposite thymine in a DNA template. | ||
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| - | Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing pyrimidine transition mutations.,Zhang F, Tsunoda M, Suzuki K, Kikuchi Y, Wilkinson O, Millington CL, Margison GP, Williams DM, Czarina Morishita E, Takenaka A Nucleic Acids Res. 2013 Apr 10. PMID:23580550<ref>PMID:23580550</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | == References == | ||
| - | <references/> | ||
| __TOC__ | __TOC__ | ||
| </StructureSection> | </StructureSection> | ||
| - | [[Category: Millington | + | [[Category: Large Structures]] | 
| - | [[Category: Morishita | + | [[Category: Millington CL]] | 
| - | [[Category: Suzuki | + | [[Category: Morishita EC]] | 
| - | [[Category: Takenaka | + | [[Category: Suzuki K]] | 
| - | [[Category: Tsunoda | + | [[Category: Takenaka A]] | 
| - | [[Category: Wilkinson | + | [[Category: Tsunoda M]] | 
| - | [[Category: Williams | + | [[Category: Wilkinson O]] | 
| - | [[Category: Zhang | + | [[Category: Williams DM]] | 
| - | + | [[Category: Zhang F]] | |
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Current revision
Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing transition mutation
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