 |
PDBsum entry 6o2l
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
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.
|
|
|
Authors
|
|
W.Liu,
C.Lin,
G.Wu,
J.Dai,
T.C.Chang,
D.Yang.
|
|
|
Ref.
|
|
Nucleic Acids Res, 2019,
47,
11931-11942.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
Headers
|
|
|
|
|
|
