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380d

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Revision as of 14:46, 11 August 2016

BINDING OF THE MODIFIED DAUNORUBICIN WP401 ADJACENT TO A T-G BASE PAIR INDUCES THE REVERSE WATSON-CRICK CONFORMATION: CRYSTAL STRUCTURES OF THE WP401-TGGCCG AND WP401-CGG[BR5C]CG COMPLEXES

Structural highlights

380d is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

2'-Bromo-4'-epi-daunorubicin (alpha-manno configuration, denoted WP401) is a new anthracycline drug that exhibits promising activity toward multidrug-resistant cancer cells. We carried out X-ray diffraction analyses of the complexes formed in the presence of formaldehyde between WP401 and two DNA hexamers, TGGCCG and CGG[br5C]CG. The two complexes crystallized in different crystal lattices with respective crystal data of space group P4322, a = b = 37.20 A, c = 70.53 A and space group P43212, a = b = 37.23 A, c = 61. 96 A. These new crystal forms are different from the P41212 form of other daunorubicin/doxorubicin complexes studied previously. The refined crystal structures at approximately 2.0 A resolution revealed that the entire 2:1 drug-DNA complex is in the asymmetrical unit. Two WP401 drug molecules bind to the duplex, with the aglycones intercalated between the CpG or TpG steps and their modified daunosamines in the minor groove. As observed earlier, in the presence of formaldehyde, WP401 more readily forms a covalent adduct with (C/T)GG*:CCG than with (C/T)GC:G*CG (G* is the crosslink site), the opposite of what is seen for daunorubicin and doxorubicin. Surprisingly, the two T-G mismatched base pairs in the WP401-TGGCCG complex adopt the reverse Watson-Crick conformation, instead of the wobble conformation. The unusual T-G reverse Watson-Crick conformation may be required in order to maintain favorable stacking interactions between the base pair and the aglycone of WP401. Our results show that chemical modifications like bromo or iodo substitution on anthracycline drugs have significant effects on their DNA binding properties.

Binding of the modified daunorubicin WP401 adjacent to a T-G base pair induces the reverse Watson-Crick conformation: crystal structures of the WP401-TGGCCG and WP401-CGG[br5C]CG complexes.,Dutta R, Gao YG, Priebe W, Wang AH Nucleic Acids Res. 1998 Jun 15;26(12):3001-5. PMID:9611247^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dutta R, Gao YG, Priebe W, Wang AH. Binding of the modified daunorubicin WP401 adjacent to a T-G base pair induces the reverse Watson-Crick conformation: crystal structures of the WP401-TGGCCG and WP401-CGG[br5C]CG complexes. Nucleic Acids Res. 1998 Jun 15;26(12):3001-5. PMID:9611247

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/380d"

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 ==BINDING OF THE MODIFIED DAUNORUBICIN WP401 ADJACENT TO A T-G BASE PAIR INDUCES THE REVERSE WATSON-CRICK CONFORMATION: CRYSTAL STRUCTURES OF THE WP401-TGGCCG AND WP401-CGG[BR5C]CG COMPLEXES==
 <StructureSection load='380d' size='340' side='right' caption='[[380d]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DM8:2-BROMO-4-EPIDAUNORUBICIN'>DM8</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBR:5-BROMO-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>CBR</scene>, <scene name='pdbligand=G49:N2-METHYL-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>G49</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=380d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=380d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=380d RCSB], [http://www.ebi.ac.uk/pdbsum/380d PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=380d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=380d OCA], [http://pdbe.org/380d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=380d RCSB], [http://www.ebi.ac.uk/pdbsum/380d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=380d ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 15: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 380d" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

380d

From Proteopedia

Revision as of 14:46, 11 August 2016

BINDING OF THE MODIFIED DAUNORUBICIN WP401 ADJACENT TO A T-G BASE PAIR INDUCES THE REVERSE WATSON-CRICK CONFORMATION: CRYSTAL STRUCTURES OF THE WP401-TGGCCG AND WP401-CGG[BR5C]CG COMPLEXES

Structural highlights

Publication Abstract from PubMed

References

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