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| | ==DNA duplex containing mispair-aligned O6G-heptylene-O6G interstrand cross-link== | | ==DNA duplex containing mispair-aligned O6G-heptylene-O6G interstrand cross-link== |
| - | <StructureSection load='2lzw' size='340' side='right'caption='[[2lzw]], [[NMR_Ensembles_of_Models | 11 NMR models]]' scene=''> | + | <StructureSection load='2lzw' size='340' side='right'caption='[[2lzw]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lzw]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LZW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LZW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lzw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LZW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HP6:HEPTANE'>HP6</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n4b|1n4b]], [[1s37|1s37]], [[1xci|1xci]], [[2lzv|2lzv]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HP6:HEPTANE'>HP6</scene></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=2lzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lzw OCA], [http://pdbe.org/2lzw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lzw RCSB], [http://www.ebi.ac.uk/pdbsum/2lzw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lzw ProSAT]</span></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=2lzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lzw OCA], [https://pdbe.org/2lzw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lzw RCSB], [https://www.ebi.ac.uk/pdbsum/2lzw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lzw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Denisov, A Y]] | + | [[Category: Synthetic construct]] |
| - | [[Category: McManus, F P]] | + | [[Category: Denisov AY]] |
| - | [[Category: Noronha, A M]] | + | [[Category: McManus FP]] |
| - | [[Category: Wilds, C J]] | + | [[Category: Noronha AM]] |
| - | [[Category: Dna]] | + | [[Category: Wilds CJ]] |
| - | [[Category: Interstrand cross-link]]
| + | |
| Structural highlights
Publication Abstract from PubMed
DNA interstrand cross-links (ICL) are among the most cytotoxic lesions found in biological systems. O6-Alkylguanine DNA alkyltransferases (AGTs) are capable of removing alkylation damage from the O6-atom of 2'-deoxyguanosine and the O4-atom of thymidine. Human AGT (hAGT) has demonstrated the ability to repair an interstrand cross-linked duplex where two O6-atoms of 2'-deoxyguanosine were tethered by a butylene (XLGG4) or heptylene (XLGG7) linkage. However, the analogous ICL between the O4-atoms of thymidine was found to evade repair. ICL duplexes connecting the O4-atoms of 2'-deoxyuridine by a butylene (XLUU4) or heptylene (XLUU7) linkage have been prepared to examine the influence of the C5-methyl group on AGT-mediated repair. Both XLUU4 and XLUU7 were refractory to repair by human and E. coli (OGT and Ada-C) AGTs with comparably low muM dissociation constants for 2 : 1 or 4 : 1 AGT/DNA stoichiometries. The solution structures of two heptylene linked DNA duplexes (CGAAAYTTTCG)2, XLUU7 (Y = dU) and XLGG7 (Y = dG), were solved and the global structures were virtually identical with a RMSD of 1.22 A. The ICL was found to reside in the major groove for both duplexes. The linkage adopts an E conformation about the C4-O4 bond for XLUU7 whereas a Z conformation about the C6-O6 bond was observed for XLGG7. This E versus Z conformation may partially account for hAGTs discrimination towards the repair of these ICL, supported by the crystal structures of hAGT with various substrates which have been observed to adopt a Z conformation. In addition, a higher mobility at the ICL site for XLUU7 is observed relative to XLGG7 that may play a role in repair by hAGT. Taken together, these findings provide insights on the AGT-mediated repair of cytotoxic ICL in terms of its processing capability and substrate specificity.
Structural basis of interstrand cross-link repair by O6-alkylguanine DNA alkyltransferase.,Denisov AY, McManus FP, O'Flaherty DK, Noronha AM, Wilds CJ Org Biomol Chem. 2017 Sep 22. doi: 10.1039/c7ob02093g. PMID:28937154[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Denisov AY, McManus FP, O'Flaherty DK, Noronha AM, Wilds CJ. Structural basis of interstrand cross-link repair by O6-alkylguanine DNA alkyltransferase. Org Biomol Chem. 2017 Sep 22. doi: 10.1039/c7ob02093g. PMID:28937154 doi:http://dx.doi.org/10.1039/c7ob02093g
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