2lzv

<StructureSection load='2lzv' size='340' side='right'caption='[[2lzv]], [[NMR_Ensembles_of_Models | 11 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[2lzv]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LZV FirstGlance]. <br>

</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'>[https://proteopedia.org/fgij/fg.htm?mol=2lzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lzv OCA], [https://pdbe.org/2lzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lzv RCSB], [https://www.ebi.ac.uk/pdbsum/2lzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lzv ProSAT]</span></td></tr>

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== 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<ref>PMID:28937154</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 2lzv" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Denisov, A Y]]

[[Category: McManus, F P]]

[[Category: Noronha, A M]]

[[Category: Wilds, C J]]

[[Category: Interstrand cross-link]]