5zev

Solution structure of G-quadruplex formed in vegfr-2 proximal promoter sequence

spinqualitylabelsall models 5zev Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5zev is a 1 chain structure with sequence from Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 (G1) 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 degrees C, the scaffold of this quadruplex is stabilized by one G-tetrad plane stacking with one nonstandard base pair, G3-C8, 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. A putative G-quadruplex structure in the proximal promoter of vegfr-2 has implications for drug design to inhibit tumor angiogenesis.,Liu Y, Lan W, Wang C, Cao C J Biol Chem. 2018 Apr 17. pii: RA118.002666. doi: 10.1074/jbc.RA118.002666. PMID:29666187 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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