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| - | [[Image:1d38.gif|left|200px]] | |
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| - | <!--
| + | ==INFLUENCE OF AGLYCONE MODIFICATIONS ON THE BINDING OF ANTHRACYCLINE DRUGS TO DNA: THE MOLECULAR STRUCTURE OF IDARUBICIN AND 4-O-DEMETHYL-11-DEOXYDOXORUBICIN COMPLEXED TO D(CGATCG)== |
| - | The line below this paragraph, containing "STRUCTURE_1d38", creates the "Structure Box" on the page.
| + | <StructureSection load='1d38' size='340' side='right'caption='[[1d38]], [[Resolution|resolution]] 1.70Å' 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'>[[1d38]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D38 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]] 1.7Å</td></tr> |
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| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DM5:IDARUBICIN'>DM5</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | {{STRUCTURE_1d38| PDB=1d38 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1d38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d38 OCA], [https://pdbe.org/1d38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d38 RCSB], [https://www.ebi.ac.uk/pdbsum/1d38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d38 ProSAT]</span></td></tr> |
| - | | + | </table> |
| - | '''INFLUENCE OF AGLYCONE MODIFICATIONS ON THE BINDING OF ANTHRACYCLINE DRUGS TO DNA: THE MOLECULAR STRUCTURE OF IDARUBICIN AND 4-O-DEMETHYL-11-DEOXYDOXORUBICIN COMPLEXED TO D(CGATCG)'''
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | | + | [[Category: Large Structures]] |
| - | ==Overview== | + | [[Category: Gao Y-G]] |
| - | X-ray diffraction analyses of the complexes between two anthracycline antitumor compounds, idarubicin (IDR) and 4-O-demethyl-11-deoxydoxorubicin (ddDOX), with the DNA hexamer d(CGATCG) provided the detailed three-dimensional molecular structures at 1.7 A and 1.8 A resolution, respectively. Their structures have been refined with the constrained refinement procedure to final R-factors of 0.188 (1724 reflections for IDR) and 0.179 (1247 reflections for ddDOX). The overall structures of both complexes are similar to those of the previously studied DAU- and DOX-DNA complexes. In both complexes, two IDR (and ddDOX) molecules bind to the DNA hexamer double helix with the elongated aglycone chromophore intercalated between the CpG steps at both ends of the helix. The aglycone chromophore spans the GC Watson-Crick base pairs with its amino sugar lying in the minor groove where little structural difference is seen, compared with the daunorubicin-d(CGATCG) and doxorubicin-d(CGATCG) complexes. In contrast, the missing C4 methoxy of IDR and the missing methyl group at the O4 position of ddDOX result in a different binding surface in the major groove. The O4 hydroxyl group is capable of receiving and/or donating a hydrogen bond to proteins that bind to the drug-DNA complex. The missing O11 hydroxyl group in ring B creates an empty space in the intercalation cavity between the two GC base pairs, which appears to affect the stacking interactions between the aglycone and the DNA base pairs. Those structural changes in the major groove of the drug-DNA complexes due to the modifications of the aglycone chromophore may be responsible in part for the difference in their biological activities.
| + | [[Category: Wang AH-J]] |
| - | | + | |
| - | ==About this Structure== | + | |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D38 OCA]. | + | |
| - | | + | |
| - | ==Reference== | + | |
| - | Influence of aglycone modifications on the binding of anthracycline drugs to DNA: the molecular structure of idarubicin and 4-O-demethyl-11-deoxydoxorubicin complexed to d(CGATCG)., Gao YG, Wang AH, Anticancer Drug Des. 1991 Jul;6(3):137-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1872945 1872945]
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| - | [[Category: Gao, Y G.]]
| + | |
| - | [[Category: Wang, A H.J.]] | + | |
| - | [[Category: Complexed with drug]] | + | |
| - | [[Category: Double helix]] | + | |
| - | [[Category: Right handed dna]] | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:24:02 2008''
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