Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter Journal Article
| Authors: | Phan, A. T.; Kuryavyi, V.; Gaw, H. Y.; Patel, D. J. |
| Article Title: | Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter |
| Abstract: | 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. |
| Keywords: | dna binding protein; promoter region; genetics; dna-binding proteins; metabolism; tumor markers, biological; tumor marker; physiology; chemistry; dna; guanine; genes, myc; tumor suppressor proteins; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; models, molecular; chemical structure; molecular structure; protein folding; tumor suppressor protein; oncogene myc; regulatory sequence; regulatory elements, transcriptional; phosphopyruvate hydratase; promoter regions (genetics); porphyrin; porphyrins; enolase; quadruplex dna; eno1 protein, human; tetra(4 n methylpyridyl)porphine; tetra(4-n-methylpyridyl)porphine |
| Journal Title: | Nature Chemical Biology |
| Volume: | 1 |
| Issue: | 3 |
| ISSN: | 1552-4450 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-08-01 |
| Start Page: | 167 |
| End Page: | 173 |
| Language: | English |
| DOI: | 10.1038/nchembio723 |
| PUBMED: | 16408022 |
| PROVIDER: | scopus |
| PMCID: | PMC4690526 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 121" - "Export Date: 24 October 2012" - "Source: Scopus" |
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