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4itd
From Proteopedia
(Difference between revisions)
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| - | + | ==Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing transition mutation== | |
| - | + | <StructureSection load='4itd' size='340' side='right' caption='[[4itd]], [[Resolution|resolution]] 1.94Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4itd]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ITD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ITD FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HT:2-(4-HYDROXYPHENYL)-5-(4-METHYL-1-PIPERAZINYL)-2,5-BI-BENZIMIDAZOLE'>HT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=C6G:6-(CARBOXYMETHOXY)-9-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)-9H-PURIN-2-AMINE'>C6G</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ij0|4ij0]]</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=4itd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4itd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4itd RCSB], [http://www.ebi.ac.uk/pdbsum/4itd PDBsum]</span></td></tr> | ||
| + | </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. | ||
| - | + | 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> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Millington, C L | + | == References == |
| - | [[Category: Morishita, E C | + | <references/> |
| - | [[Category: Suzuki, K | + | __TOC__ |
| - | [[Category: Takenaka, A | + | </StructureSection> |
| - | [[Category: Tsunoda, M | + | [[Category: Millington, C L]] |
| - | [[Category: Wilkinson, O | + | [[Category: Morishita, E C]] |
| - | [[Category: Williams, D M | + | [[Category: Suzuki, K]] |
| - | [[Category: Zhang, F | + | [[Category: Takenaka, A]] |
| + | [[Category: Tsunoda, M]] | ||
| + | [[Category: Wilkinson, O]] | ||
| + | [[Category: Williams, D M]] | ||
| + | [[Category: Zhang, F]] | ||
[[Category: Damaged dna]] | [[Category: Damaged dna]] | ||
[[Category: Dna]] | [[Category: Dna]] | ||
[[Category: Mutagenesis]] | [[Category: Mutagenesis]] | ||
[[Category: O6-carboxymethylguanine]] | [[Category: O6-carboxymethylguanine]] | ||
Revision as of 13:08, 4 January 2015
Structures of DNA duplexes containing O6-carboxymethylguanine, a lesion associated with gastrointestinal cancer, reveal a mechanism for inducing transition mutation
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