6AU4

Crystal structure of the major quadruplex formed in the human c-MYC promoter

6AU4 の概要

• エントリーDOI: 10.2210/pdb6au4/pdb
• 分子名称: DNA (5'-D(*TP*GP*AP*GP*GP*GP*TP*GP*GP*GP*TP*AP*GP*GP*GP*TP*GP*GP*GP*TP*AP*A)-3'), POTASSIUM ION (3 entities in total)
• 機能のキーワード: oncogene, quadruplex, c-myc, promoter, dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14251.61

構造登録者

Stump, S.,Mou, T.C.,Sprang, S.R.,Natale, N.R.,Beall, H.D. (登録日: 2017-08-30, 公開日: 2018-09-12, 最終更新日: 2023-10-04)

主引用文献

Stump, S.,Mou, T.C.,Sprang, S.R.,Natale, N.R.,Beall, H.D.
Crystal structure of the major quadruplex formed in the promoter region of the human c-MYC oncogene.
PLoS ONE, 13:e0205584-e0205584, 2018

PubMed Abstract: The c-MYC oncogene mediates multiple tumor cell survival pathways and is dysregulated or overexpressed in the majority of human cancers. The NHE III1 region of the c-MYC promoter forms a DNA quadruplex. Stabilization of this structure with small molecules has been shown to reduce expression of c-MYC, and targeting the c-MYC quadruplex has become an emerging strategy for development of antitumor compounds. Previous solution NMR studies of the c-MYC quadruplex have assigned the major conformer and topology of this important target, however, regions outside the G-quartet core were not as well-defined. Here, we report a high-resolution crystal structure (2.35 Å) of the major quadruplex formed in the NHE III1 region of the c-MYC promoter. The crystal structure is in general agreement with the solution NMR structure, however, key differences are observed in the position of nucleotides outside the G-quartet core. The crystal structure provides an alternative model that, along with comparisons to other reported quadruplex crystal structures, will be important to the rational design of selective compounds. This work will aid in development of ligands to target the c-MYC promoter quadruplex with the goal of creating novel anticancer therapies.

PubMed: 30312328
DOI: 10.1371/journal.pone.0205584

実験手法

X-RAY DIFFRACTION (2.35 Å)