2a5p

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2a5p

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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

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