1fj5: Difference between revisions

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[[Image:1fj5.gif|left|200px]]
{{Seed}}
[[Image:1fj5.png|left|200px]]


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{{STRUCTURE_1fj5|  PDB=1fj5  |  SCENE=  }}  
{{STRUCTURE_1fj5|  PDB=1fj5  |  SCENE=  }}  


'''TAMOXIFEN-DNA ADDUCT'''
===TAMOXIFEN-DNA ADDUCT===




==Overview==
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The non-steroidal anti-estrogen tamoxifen [TAM] has been in clinical use over the last two decades as a potent adjunct chemotherapeutic agent for treatment of breast cancer. It has also been given prophylactically to women with a strong family history of breast cancer. However, tamoxifen treatment has also been associated with increased endometrial cancer, possibly resulting from the reaction of metabolically activated tamoxifen derivatives with cellular DNA. Such DNA adducts can be mutagenic and the activities of isomeric adducts may be conformation-dependent. We therefore investigated the high resolution NMR solution conformation of one covalent adduct (cis-isomer, S-epimer of [TAM]G) formed from the reaction of tamoxifen [TAM] to N(2)-of guanine in the d(C-[TAM]G-C).d(G-C-G) sequence context at the 11-mer oligonucleotide duplex level. Our NMR results establish that the S-cis [TAM]G lesion is accomodated within a widened minor groove without disruption of the Watson-Crick [TAM]G. C and flanking Watson-Crick G.C base-pairs. The helix axis of the bound DNA oligomer is bent by about 30 degrees and is directed away from the minor groove adduct site. The presence of such a bulky [TAM]G adduct with components of the TAM residue on both the 5'- and the 3'-side of the modified base could compromise the fidelity of the minor groove polymerase scanning machinery.
The line below this paragraph, {{ABSTRACT_PUBMED_10970740}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 10970740 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10970740}}


==About this Structure==
==About this Structure==
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FJ5 OCA].  
Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FJ5 OCA].  


==Reference==
==Reference==
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[[Category: Localized helical perturbation]]
[[Category: Localized helical perturbation]]
[[Category: Widened minor groove]]
[[Category: Widened minor groove]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:23:21 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:21:05 2008''

Revision as of 00:21, 1 July 2008

File:1fj5.png

Template:STRUCTURE 1fj5

TAMOXIFEN-DNA ADDUCT

Template:ABSTRACT PUBMED 10970740

About this Structure

Full experimental information is available from OCA.

Reference

Accomodation of S-cis-tamoxifen-N(2)-guanine adduct within a bent and widened DNA minor groove., Shimotakahara S, Gorin A, Kolbanovskiy A, Kettani A, Hingerty BE, Amin S, Broyde S, Geacintov N, Patel DJ, J Mol Biol. 2000 Sep 15;302(2):377-93. PMID:10970740

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