2a5p
From Proteopedia
(New page: 200px<br /><applet load="2a5p" size="350" color="white" frame="true" align="right" spinBox="true" caption="2a5p" /> '''Monomeric parallel-stranded DNA tetraplex wi...) |
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==Overview== | ==Overview== | ||
| - | It has been widely accepted that DNA can adopt other biologically relevant | + | It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Gaw, H | + | [[Category: Gaw, H Y.]] |
| - | [[Category: Kuryavyi, V | + | [[Category: Kuryavyi, V V.]] |
| - | [[Category: Patel, D | + | [[Category: Patel, D J.]] |
| - | [[Category: Phan, A | + | [[Category: Phan, A T.]] |
[[Category: monomeric parallel-stranded quadruplex; c-myc promoter 3+1 g-tetrad; single nucleotide chain reversal loop; gag triad; gaag loop]] | [[Category: monomeric parallel-stranded quadruplex; c-myc promoter 3+1 g-tetrad; single nucleotide chain reversal loop; gag triad; gaag loop]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:23:52 2008'' |
Revision as of 14:23, 21 February 2008
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Monomeric parallel-stranded DNA tetraplex with snap-back 3+1 3' G-tetrad, single-residue chain reversal loops, GAG triad in the context of GAAG diagonal loop, NMR, 8 struct.
Overview
It has been widely accepted that DNA can adopt other biologically relevant structures beside the Watson-Crick double helix. One recent important example is the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found in the MYC (or c-myc) promoter region, which regulates the transcription of the MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we report the first structure of a DNA fragment containing five guanine tracts from this region. An unusual G-quadruplex fold, which was derived from NMR restraints using unambiguous model-independent resonance assignment approaches, involves a core of three stacked guanine tetrads formed by four parallel guanine tracts with all anti guanines and a snapback 3'-end syn guanine. We have determined the structure of the complex formed between this G-quadruplex and TMPyP4. This structural information, combined with details of small-molecule interaction, provides a platform for the design of anticancer drugs targeting multi-guanine-tract sequences that are found in the MYC and other oncogenic promoters, as well as in telomeres.
About this Structure
2A5P is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter., Phan AT, Kuryavyi V, Gaw HY, Patel DJ, Nat Chem Biol. 2005 Aug;1(3):167-73. Epub 2005 Jul 17. PMID:16408022
Page seeded by OCA on Thu Feb 21 16:23:52 2008
