385d

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FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)

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Categories: Large Structures | Cirilli M | Ettorre A | Ughetto G

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-[[Image:385d.jpg|left|200px]]<br /><applet load="385d" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="385d, resolution 1.600&Aring;" />
-'''FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)'''<br />
-==Overview==
+==FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)==
-The cyanomorpholino analogue of antitumor anthracycline doxorubicin, possesses an intense potency and differs from the parent compound in, cross-resistance and other biological properties. The induction by, cyanomorpholinodoxorubicin of both DNA cross-links and strand scission, suggests an altered mode of action relative to doxorubicin with a, different DNA-interacting capacity. We have co-crystallized, 3'-(3-cyano-4-morpholinyl)-3'-desaminodoxorubicin (CMD) with the DNA, hexamer d(CGATCG) and have determined the crystal structure at 0.16-nm, resolution. The complex crystallizes in the space group P4(1)2(1)2 and is, similar to the previously reported anthracycline/DNA structures, with the, drug intercalated at the CpG step, forming hydrogen bonds with the guanine, residue. The structure reveals that the morpholino moiety has undergone a, major rearrangement with loss of the cyano group and opening of the, morpholino ring. The compound actually bound to DNA in the complex, resembles N-(2-hydroxyethyl)doxorubicin, which was previously identified, as a hydrolysis product of CMD. No DNA alkylation has been observed., However, the structure shows that the active site of the morpholino ring, after dissociation of the cyano group, lies in the minor groove in, proximity of the A/T base pair. This may indicate that a C/G base pair, next to the intercalation site, with NH2 group in the minor groove, is, required for DNA alkylation.
+<StructureSection load='385d' size='340' side='right'caption='[[385d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[385d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=385D FirstGlance]. <br>
-D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NOD:'>NOD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=385D 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]] 1.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NOD:N-ETHYLHYDROXY-DOXORUBICIN'>NOD</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=385d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=385d OCA], [https://pdbe.org/385d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=385d RCSB], [https://www.ebi.ac.uk/pdbsum/385d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=385d ProSAT]</span></td></tr>
-Degradation of the morpholino ring in the crystal structure of cyanomorpholinodoxorubicin complexed with d(CGATCG)., Ettorre A, Cirilli M, Ughetto G, Eur J Biochem. 1998 Dec 1;258(2):350-4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9874199 9874199]
+</table>
-[[Category: Protein complex]]
+__TOC__
-[[Category: Cirilli, M.]]
+</StructureSection>
-[[Category: Ettorre, A.]]
+[[Category: Large Structures]]
-[[Category: Ughetto, G.]]
+[[Category: Cirilli M]]
-[[Category: NOD]]
+[[Category: Ettorre A]]
-[[Category: complexed with drug]]
+[[Category: Ughetto G]]
-[[Category: double helix]]
-[[Category: right handed dna]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:37:32 2008''

385d

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FORMATION OF A NEW COMPOUND IN THE CRYSTAL STRUCTURE OF CYANOMORPHOLINODOXORUBICIN COMPLEXED WITH D(CGATCG)

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