6O2L

NMR structure of the 2:1 complex of a carbazole derivative BMVC bound to c-MYC G-quadruplex

6O2L の概要

• エントリーDOI: 10.2210/pdb6o2l/pdb
• NMR情報: BMRB: 30577
• 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'), 3,6-bis[(E)-2-(1-methylpyridin-1-ium-4-yl)ethenyl]-9H-carbazole (2 entities in total)
• 機能のキーワード: g-quadruplex dna, drug-dna complex, bmvc, dna
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7815.55

構造登録者

Lin, C.,Liu, W.,Yang, D. (登録日: 2019-02-24, 公開日: 2019-10-23, 最終更新日: 2024-05-01)

主引用文献

Liu, W.,Lin, C.,Wu, G.,Dai, J.,Chang, T.C.,Yang, D.
Structures of 1:1 and 2:1 complexes of BMVC and MYC promoter G-quadruplex reveal a mechanism of ligand conformation adjustment for G4-recognition.
Nucleic Acids Res., 47:11931-11942, 2019

PubMed Abstract: BMVC is the first fluorescent probe designed to detect G-quadruplexes (G4s) in vivo. The MYC oncogene promoter forms a G4 (MycG4) which acts as a transcription silencer. Here, we report the high-affinity and specific binding of BMVC to MycG4 with unusual slow-exchange rates on the NMR timescale. We also show that BMVC represses MYC in cancer cells. We determined the solution structures of the 1:1 and 2:1 BMVC-MycG4 complexes. BMVC first binds the 5'-end of MycG4 to form a 1:1 complex with a well-defined structure. At higher ratio, BMVC also binds the 3'-end to form a second complex. In both complexes, the crescent-shaped BMVC recruits a flanking DNA residue to form a BMVC-base plane stacking over the external G-tetrad. Remarkably, BMVC adjusts its conformation to a contracted form to match the G-tetrad for an optimal stacking interaction. This is the first structural example showing the importance of ligand conformational adjustment in G4 recognition. BMVC binds the more accessible 5'-end with higher affinity, whereas sequence specificity is present at the weaker-binding 3'-site. Our structures provide insights into specific recognition of MycG4 by BMVC and useful information for design of G4-targeted anticancer drugs and fluorescent probes.

PubMed: 31740959
DOI: 10.1093/nar/gkz1015

実験手法

SOLUTION NMR