2lzv
From Proteopedia
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==DNA duplex containing mispair-aligned O4U-heptylene-O4U interstrand cross-link== | ==DNA duplex containing mispair-aligned O4U-heptylene-O4U interstrand cross-link== | ||
<StructureSection load='2lzv' size='340' side='right' caption='[[2lzv]], [[NMR_Ensembles_of_Models | 11 NMR models]]' scene=''> | <StructureSection load='2lzv' size='340' side='right' caption='[[2lzv]], [[NMR_Ensembles_of_Models | 11 NMR models]]' scene=''> | ||
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DU:2-DEOXYURIDINE-5-MONOPHOSPHATE'>DU</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DU:2-DEOXYURIDINE-5-MONOPHOSPHATE'>DU</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n4b|1n4b]], [[1s37|1s37]], [[1xci|1xci]], [[2lzw|2lzw]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n4b|1n4b]], [[1s37|1s37]], [[1xci|1xci]], [[2lzw|2lzw]]</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=2lzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lzv OCA], [http://pdbe.org/2lzv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lzv RCSB], [http://www.ebi.ac.uk/pdbsum/2lzv PDBsum]</span></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=2lzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lzv OCA], [http://pdbe.org/2lzv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lzv RCSB], [http://www.ebi.ac.uk/pdbsum/2lzv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lzv ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:28937154</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2lzv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 09:17, 4 October 2017
DNA duplex containing mispair-aligned O4U-heptylene-O4U interstrand cross-link
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