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New page: left|200px<br /><applet load="1nab" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nab, resolution 2.15Å" /> '''The crystal structur...
 
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[[Image:1nab.gif|left|200px]]<br /><applet load="1nab" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1nab, resolution 2.15&Aring;" />
'''The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes'''<br />


==Overview==
==The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes==
The crystal structure of the complex formed between the anthracycline, antibiotic 3'-deamino-3'- hydroxy-4'-(O-L-daunosaminyl)-4-demethoxydoxo, rubicin (MEN 10755), an active disaccharide analogue of doxorubicin, and, the DNA hexamer d(CGATCG) has been solved to a resolution of 2.1 A. MEN, 10755 exhibits a broad spectrum of antitumor activities, comparable with, that of the parent compound, but there are differences in the mechanism of, action as it is active in doxorubicin-resistant tumors and is more, effective in stimulating topoisomerase DNA cleavage. The structure is, similar to previously crystallised anthracycline- DNA complexes. However, two different binding sites arise from drug intercalation so that the two, halves of the self-complementary duplex are no longer equivalent. In one, site both sugar rings lie in the minor groove. In the other site the, second sugar protrudes out from the DNA helix and is linked, through, hydrogen bonds, to guanine of a symmetry-related DNA molecule. This is the, first structure of an anthracycline-DNA complex where an interaction of, the drug with a second DNA helix is observed. We discuss the present, findings with respect to the relevance of the amino group for DNA binding, and to the potential role played by the second sugar in the interactions, with topoisomerases or other cellular targets.
<StructureSection load='1nab' size='340' side='right'caption='[[1nab]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1nab]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NAB FirstGlance]. <br>
1NAB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with 44D as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NAB OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=44D:7-[5-(4-AMINO-5-HYDROXY-6-METHYL-TETRAHYDRO-PYRAN-2-YLOXY)-4-HYDROXY-6-METHYL-TETRAHYDRO-PYRAN-2-YLOXY]-6,9,11-TRIHYDROXY-9-(2-HYDROXY-ACETYL)-7,8,9,10-TETRAHYDRO-NAPHTHACENE-5,12-DIONE'>44D</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nab OCA], [https://pdbe.org/1nab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nab RCSB], [https://www.ebi.ac.uk/pdbsum/1nab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nab ProSAT]</span></td></tr>
The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes., Temperini C, Messori L, Orioli P, Di Bugno C, Animati F, Ughetto G, Nucleic Acids Res. 2003 Mar 1;31(5):1464-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12595554 12595554]
</table>
[[Category: Protein complex]]
__TOC__
[[Category: Animati, F.]]
</StructureSection>
[[Category: Bugno, C.Di.]]
[[Category: Large Structures]]
[[Category: Messori, L.]]
[[Category: Animati F]]
[[Category: Orioli, P.]]
[[Category: Di Bugno C]]
[[Category: Temperini, C.]]
[[Category: Messori L]]
[[Category: Ughetto, G.]]
[[Category: Orioli P]]
[[Category: 44D]]
[[Category: Temperini C]]
[[Category: complexed with drug]]
[[Category: Ughetto G]]
[[Category: double helix]]
[[Category: right handed dna]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:49:51 2007''

Latest revision as of 07:54, 14 February 2024

The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes

1nab, resolution 2.15Å

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