278d

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(New page: 200px<br /><applet load="278d" size="350" color="white" frame="true" align="right" spinBox="true" caption="278d, resolution 1.800&Aring;" /> '''SUBSTITUTIONS AT C2...)
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[[Image:278d.gif|left|200px]]<br /><applet load="278d" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="278d, resolution 1.800&Aring;" />
 
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'''SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY'''<br />
 
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==Overview==
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==SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY==
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In the search for new generations of anthracycline drugs, lower cytotoxic, side effect and higher activity toward resistant cancer cells are two, major goals. A new anthracycline drug, WP401 (2'-bromo-4'-epidaunorubicin, alpha-manno configuration), exhibits promising activity toward, multidrug-resistant cells. In contrast, the related compound WP400, (2'-bromo-4'-epidaunorubicin, alpha-gluco configuration), is significantly, less cytotoxic. To establish the structural and molecular bases of this, observation, we performed X-ray diffraction analyses of the complexes, between WP401 and four DNA hexamers CGTACG, CGATCG, CGCGCG, and CGGCCG., Their crystal data (space group P4(1)2(1)2, a = b approximately 2.8 nm, c, approximately 5.3 nm) are similar to those of other, daunorubicin/doxorubicin complexes. The refined crystal structures at, 0.18-nm resolution revealed that two WP401 drug molecules bind to the, duplex, with the aglycons intercalated between the CpG steps and their, modified daunosamines in the minor groove. The bulky bromine atom at the, C2' position caused the daunosamine of the bound WP401 to adopt a, different conformation from that of the bound daunorubicin. In the, presence of formaldehyde, WP401 formed a covalent adduct with CGGCCG more, readily than with CGCGCG. This is the opposite of what is seen for, daunorubicin and doxorubicin. Thus modifications at the C2' position of, daunosamine modulate the sequence specificity of the, formaldehyde-crosslinking reactions between anthracyclines and DNA.
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<StructureSection load='278d' size='340' side='right'caption='[[278d]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[278d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=278D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=278D FirstGlance]. <br>
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278D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=DM8:'>DM8</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=278D OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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=DM8:2-BROMO-4-EPIDAUNORUBICIN'>DM8</scene>, <scene name='pdbligand=G49:N2-METHYL-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>G49</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=278d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=278d OCA], [https://pdbe.org/278d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=278d RCSB], [https://www.ebi.ac.uk/pdbsum/278d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=278d ProSAT]</span></td></tr>
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Substitutions at C2' of daunosamine in the anticancer drug daunorubicin alter its DNA-binding sequence specificity., Gao YG, Priebe W, Wang AH, Eur J Biochem. 1996 Sep 1;240(2):331-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8841395 8841395]
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</table>
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[[Category: Protein complex]]
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__TOC__
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[[Category: Gao, Y.G.]]
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</StructureSection>
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[[Category: Priebe, W.]]
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[[Category: Large Structures]]
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[[Category: Wang, A.H.J.]]
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[[Category: Gao Y-G]]
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[[Category: DM8]]
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[[Category: Priebe W]]
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[[Category: complexed with drug]]
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[[Category: Wang AH-J]]
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[[Category: double helix]]
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[[Category: modified]]
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[[Category: right handed dna]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 17:50:22 2008''
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Current revision

SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY

PDB ID 278d

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