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1xav

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{{STRUCTURE_1xav| PDB=1xav | SCENE= }}
{{STRUCTURE_1xav| PDB=1xav | SCENE= }}
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'''Solution Structure of the Biologically Relevant G-Quadruplex Element in the Human c-MYC Promoter.'''
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===Solution Structure of the Biologically Relevant G-Quadruplex Element in the Human c-MYC Promoter.===
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==Overview==
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The nuclease hypersensitivity element III(1) (NHE III(1)) of the c-MYC promoter strongly controls the transcriptional activity of the c-MYC oncogene. The purine-rich strand of the NHE III(1) element has been shown to be a silencer element for c-MYC transcription upon formation of a G-quadruplex structure. We have determined the predominant G-quadruplex structure of this silencer element in potassium solution by NMR. The G-quadruplex structure adopts an intramolecular parallel-stranded quadruplex conformation with three guanine tetrads and three side loops, including two single-nucleotide side loops and one double-nucleotide side loop, that connect the four guanine strands. The three side loops are very stable and well-defined. The 3'-flanking sequence forms a stable fold-back stacking conformation capping the top end of the G-quadruplex structure. The 5'-flanking A and G bases cap the bottom end of the G-quadruplex, with the adenine stacking very well with the bottom tetrad. This paper reports the first solution structure of a G-quadruplex found to form in the promoter region of an oncogene (c-MYC). This G-quadruplex structure is extremely stable, with a similar melting temperature (&gt;85 degrees C) to that of the wild-type 27-mer purine-rich NHE III(1) sequence of the c-MYC promoter. This predominant quadruplex structure has been shown to be biologically relevant, and the structural information revealed in this research provides an important basis for the design of new drug candidates that specifically target the c-MYC G-quadruplex structure and modulate gene expression.
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(as it appears on PubMed at http://www.pubmed.gov), where 15697230 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15697230}}
==About this Structure==
==About this Structure==
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XAV OCA].
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Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XAV OCA].
==Reference==
==Reference==
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[[Category: C-myc promoter dna]]
[[Category: C-myc promoter dna]]
[[Category: Parallel stranded guanine-quadruplex,nmr structure]]
[[Category: Parallel stranded guanine-quadruplex,nmr structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:47:48 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:21:50 2008''

Revision as of 11:21, 27 July 2008

Image:1xav.png

Template:STRUCTURE 1xav

Solution Structure of the Biologically Relevant G-Quadruplex Element in the Human c-MYC Promoter.

Template:ABSTRACT PUBMED 15697230

About this Structure

Full experimental information is available from OCA.

Reference

Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. Implications for G-quadruplex stabilization., Ambrus A, Chen D, Dai J, Jones RA, Yang D, Biochemistry. 2005 Feb 15;44(6):2048-58. PMID:15697230

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