Back to Search
Start Over
A putative G-quadruplex structure in the proximal promoter of
- Source :
- The Journal of biological chemistry. 293(23)
- Publication Year :
- 2018
-
Abstract
- Tumor angiogenesis is mainly regulated by vascular endothelial growth factor (VEGF) produced by cancer cells. It is active on the endothelium via VEGF receptor 2 (VEGFR-2). G-quadruplexes are DNA secondary structures formed by guanine-rich sequences, for example, within gene promoters where they may contribute to transcriptional activity. The proximal promoter of VEGFR-2 contains a G-quadruplex, which has been suggested to interact with small molecules that inhibit VEGFR-2 expression and thereby tumor angiogenesis. However, its structure is not known. Here, we determined its NMR solution structure, which is composed of three stacked G-tetrads containing three syn guanines. The first guanine (G(1)) is positioned within the central G-tetrad. We also observed that a noncanonical, V-shaped loop spans three G-tetrad planes, including no bridging nucleotides. A long and diagonal loop, which includes six nucleotides, connects reversal double chains. With a melting temperature of 54.51 °C, the scaffold of this quadruplex is stabilized by one G-tetrad plane stacking with one nonstandard bp, G(3)–C(8), whose bases interact with each other through only one hydrogen bond. In summary, the NMR solution structure of the G-quadruplex in the proximal promoter region of the VEGFR-2 gene reported here has uncovered its key features as a potential anticancer drug target.
- Subjects :
- 0301 basic medicine
Models, Molecular
Guanine
Angiogenesis
Angiogenesis Inhibitors
010402 general chemistry
G-quadruplex
01 natural sciences
Biochemistry
Small Molecule Libraries
03 medical and health sciences
chemistry.chemical_compound
Neoplasms
Humans
Nucleotide
Promoter Regions, Genetic
Molecular Biology
chemistry.chemical_classification
Base Sequence
Neovascularization, Pathologic
Promoter
Kinase insert domain receptor
Cell Biology
Vascular Endothelial Growth Factor Receptor-2
0104 chemical sciences
Cell biology
Vascular endothelial growth factor
G-Quadruplexes
030104 developmental biology
chemistry
Drug Design
Additions and Corrections
DNA
Molecular Biophysics
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 293
- Issue :
- 23
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....086ddeed720f50e8852589c48193c215