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| - | [[Image:1qda.gif|left|200px]] | |
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| - | <!--
| + | ==Crystal structure of epidoxorubicin-formaldehyde virtual crosslink of DNA== |
| - | The line below this paragraph, containing "STRUCTURE_1qda", creates the "Structure Box" on the page.
| + | <StructureSection load='1qda' size='340' side='right'caption='[[1qda]], [[Resolution|resolution]] 1.60Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1qda]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QDA FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | -->
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DM6:4-EPIDOXORUBICIN'>DM6</scene>, <scene name='pdbligand=G49:N2-METHYL-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>G49</scene></td></tr> |
| - | {{STRUCTURE_1qda| PDB=1qda | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qda OCA], [https://pdbe.org/1qda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qda RCSB], [https://www.ebi.ac.uk/pdbsum/1qda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qda ProSAT]</span></td></tr> |
| - | | + | </table> |
| - | '''CRYSTAL STRUCTURE OF EPIDOXORUBICIN-FORMALDEHYDE VIRTUAL CROSSLINK OF DNA''' | + | __TOC__ |
| - | | + | </StructureSection> |
| - | | + | [[Category: Large Structures]] |
| - | ==Overview== | + | [[Category: Harrington DJ]] |
| - | Epidoxorubicin and daunorubicin are proposed to be cytotoxic to tumor cells by catalyzing production of formaldehyde through redox cycling and using the formaldehyde for covalent attachment to DNA at G bases. The crystal structure of epidoxorubicin covalently bound to a d(CGCGCG) oligomer was determined to 1.6 A resolution. The structure reveals slightly distorted B-form DNA bearing two molecules of epidoxorubicin symmetrically intercalated at the termini, with each covalently attached from its N3' to N2 of a G base via a CH2 group from the formaldehyde. The structure is analogous to daunorubicin covalently bound to d(CGCGCG) determined previously, except for additional hydrogen bonding from the epimeric O4' to O2 of a C base. The role of drug-DNA covalent bonding in cells was investigated with synthetic epidoxorubicin-formaldehyde conjugate (Epidoxoform) and synthetic daunorubicin-formaldehyde conjugate (Daunoform). Uptake and location of drug fluorophore in doxorubicin-resistant human breast-cancer cells (MCF-7/ADR cells) was observed by fluorescence microscopy and flow cytometry. The fluorophore of Daunoform appeared more rapidly in cells and was released more rapidly from cells than the fluorophore of Epidoxoform over a 3 h exposure period. The fluorophore appeared predominantly in the nucleus of cells treated with both conjugates. The difference in uptake is explained in terms of the slower rate of hydrolysis of Epidoxoform to the species reactive with DNA and a proposed slower release from DNA based upon the crystal structures.
| + | [[Category: Koch TH]] |
| - | | + | [[Category: Podell ER]] |
| - | ==About this Structure==
| + | [[Category: Taatjes DJ]] |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QDA OCA]. | + | |
| - | | + | |
| - | ==Reference== | + | |
| - | Crystal structure of epidoxorubicin-formaldehyde virtual crosslink of DNA and evidence for its formation in human breast-cancer cells., Podell ER, Harrington DJ, Taatjes DJ, Koch TH, Acta Crystallogr D Biol Crystallogr. 1999 Sep;55(Pt 9):1516-23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10489446 10489446]
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| - | [[Category: Harrington, D J.]]
| + | |
| - | [[Category: Koch, T H.]] | + | |
| - | [[Category: Podell, E R.]] | + | |
| - | [[Category: Taatjes, D J.]] | + | |
| - | [[Category: Double helix]] | + | |
| - | [[Category: Drug-dna complex]] | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:09:19 2008''
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