PDBsum entry 6o2l

DNA

PDB id: 6o2l

Contents

DNA/RNA

Ligands

BO6 ×2

PDB id:

6o2l

Name:

DNA

Title:

Nmr structure of the 2:1 complex of a carbazole derivative bmvc bound to c-myc g-quadruplex

Structure:

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'). Chain: a. Engineered: yes

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606

NMR struc:

20 models

Authors:

C.Lin,W.Liu,D.Yang

Key ref:

W.Liu et al. (2019). 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. PubMed id: 31740959 DOI: 10.1093/nar/gkz1015

Date:

24-Feb-19 Release date: 23-Oct-19

DNA/RNA chain

T-G-A-G-G-G-T-G-G-G-T-A-G-G-G-T-G-G-G-T-A-A 22 bases

DOI no: 10.1093/nar/gkz1015

Nucleic Acids Res 47:11931-11942 (2019)

PubMed id: 31740959

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.

W.Liu, C.Lin, G.Wu, J.Dai, T.C.Chang, D.Yang.

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.