2A5R

Complex of tetra-(4-n-methylpyridyl) porphin with monomeric parallel-stranded DNA tetraplex, snap-back 3+1 3' G-tetrad, single-residue chain reversal loops, GAG triad in the context of GAAG diagonal loop, C-MYC promoter, NMR, 6 struct.

Summary for 2A5R

• Entry DOI: 10.2210/pdb2a5r/pdb
• Related: 1D6D 1EEG 1JJP 1Y8D 2A5P
• Descriptor: 5'-D(*TP*GP*AP*GP*GP*GP*TP*GP*GP*IP*GP*AP*GP*GP*GP*TP*GP*GP*GP*GP*AP*AP*GP*G)-3', (1Z,4Z,9Z,15Z)-5,10,15,20-tetrakis(1-methylpyridin-1-ium-4-yl)-21,23-dihydroporphyrin (2 entities in total)
• Functional Keywords: monomeric parallel-stranded quadruplex; c-myc promoter 3+1 g-tetrad; single nucleotide chain reversal loop; gag triad; gaag loop, dna
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 8380.76

Authors

Phan, A.T.,Kuryavyi, V.V.,Gaw, H.Y.,Patel, D.J. (deposition date: 2005-06-30, release date: 2005-07-26, Last modification date: 2024-05-01)

Primary citation

Phan, A.T.,Kuryavyi, V.,Gaw, H.Y.,Patel, D.J.
Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter.
Nat.Chem.Biol., 1:167-173, 2005

PubMed 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.

PubMed: 16408022
DOI: 10.1038/nchembio723

Experimental method

SOLUTION NMR