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2f8u

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(New page: 200px<br /><applet load="2f8u" size="350" color="white" frame="true" align="right" spinBox="true" caption="2f8u" /> '''Solution structure of G-quadruplex formed in...)
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==Overview==
==Overview==
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BCL2 protein functions as an inhibitor of cell apoptosis and has been, found to be aberrantly expressed in a wide range of human diseases. A, highly GC-rich region upstream of the P1 promoter plays an important role, in the transcriptional regulation of BCL2. Here we report the NMR solution, structure of the major intramolecular G-quadruplex formed on the G-rich, strand of this region in K+ solution. This well-defined mixed, parallel/antiparallel-stranded G-quadruplex structure contains three, G-tetrads of mixed G-arrangements, which are connected with two lateral, loops and one side loop, and four grooves of different widths. The three, loops interact with the core G-tetrads in a specific way that defines and, stabilizes the overall G-quadruplex structure. The loop conformations are, in accord with the experimental mutation and footprinting data. The first, 3-nt loop adopts a lateral loop conformation and appears to determine the, overall folding of the BCL2 G-quadruplex. The third 1-nt, double-chain-reversal loop defines another example of a stable, parallel-stranded structural motif using the G3NG3 sequence., Significantly, the distinct major BCL2 promoter G-quadruplex structure, suggests that it can be specifically involved in gene modulation and can, be an attractive target for pathway-specific drug design.
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BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regulation of BCL2. Here we report the NMR solution structure of the major intramolecular G-quadruplex formed on the G-rich strand of this region in K+ solution. This well-defined mixed parallel/antiparallel-stranded G-quadruplex structure contains three G-tetrads of mixed G-arrangements, which are connected with two lateral loops and one side loop, and four grooves of different widths. The three loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure. The loop conformations are in accord with the experimental mutation and footprinting data. The first 3-nt loop adopts a lateral loop conformation and appears to determine the overall folding of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines another example of a stable parallel-stranded structural motif using the G3NG3 sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design.
==About this Structure==
==About this Structure==
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[[Category: nmr]]
[[Category: nmr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 19:30:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:18:53 2008''

Revision as of 15:18, 21 February 2008

Image:2f8u.gif

2f8u

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Solution structure of G-quadruplex formed in the human Bcl-2 promoter

Overview

BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regulation of BCL2. Here we report the NMR solution structure of the major intramolecular G-quadruplex formed on the G-rich strand of this region in K+ solution. This well-defined mixed parallel/antiparallel-stranded G-quadruplex structure contains three G-tetrads of mixed G-arrangements, which are connected with two lateral loops and one side loop, and four grooves of different widths. The three loops interact with the core G-tetrads in a specific way that defines and stabilizes the overall G-quadruplex structure. The loop conformations are in accord with the experimental mutation and footprinting data. The first 3-nt loop adopts a lateral loop conformation and appears to determine the overall folding of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines another example of a stable parallel-stranded structural motif using the G3NG3 sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure suggests that it can be specifically involved in gene modulation and can be an attractive target for pathway-specific drug design.

About this Structure

2F8U is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region., Dai J, Chen D, Jones RA, Hurley LH, Yang D, Nucleic Acids Res. 2006;34(18):5133-44. Epub 2006 Sep 22. PMID:16998187

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