DSSR-derived G-quadruplex features in PDB entry 6ccw
Poster "DSSR-Enabled Automatic Identification and Annotation of G-quadruplexes in the PDB" presented at the RNA2020 online meeting
Citation: before a paper dedicated to the DSSR-G4 module comes out, please cite the 2015 DSSR paper published in Nucleic Acids Research.
- Hybrid-2 form human telomeric g quadruplex in complex with epiberberine
- Lin, C., Wu, G., Wang, K., Onel, B., Sakai, S., Shao, Y., Yang, D.: (2018) "Molecular Recognition of the Hybrid-2 Human Telomeric G-Quadruplex by Epiberberine: Insights into Conversion of Telomeric G-Quadruplex Structures." Angew. Chem. Int. Ed. Engl., 57, 10888-10893.
- Human telomeres can form DNA G-quadruplex (G4), an attractive target for anticancer drugs. Human telomeric G4s bear inherent structure polymorphism, challenging for understanding specific recognition by ligands or proteins. Protoberberines are medicinal natural-products known to stabilize telomeric G4s and inhibit telomerase. Here we report epiberberine (EPI) specifically recognizes the hybrid-2 telomeric G4 predominant in physiologically relevant K+ solution and converts other telomeric G4 forms to hybrid-2, the first such example reported. Our NMR structure in K+ solution shows EPI binding induces extensive rearrangement of the previously disordered 5'-flanking and loop segments to form an unprecedented four-layer binding pocket specific to the hybrid-2 telomeric G4; EPI recruits the (-1) adenine to form a "quasi-triad" intercalated between the external tetrad and a T:T:A triad, capped by a T:T base pair. Our study provides structural basis for small-molecule drug design targeting the human telomeric G4.
- G4 notes
- 3 G-tetrads, 1 G4 helix, 1 G4 stem · 3(-Lw-Ln-P), hybrid-2(3+1), UDUU
1 glyco-bond=s-ss groove=wn-- planarity=0.262 type=other nts=4 GGGG A.DG4,A.DG12,A.DG16,A.DG22 2 glyco-bond=-s-- groove=wn-- planarity=0.153 type=planar nts=4 GGGG A.DG5,A.DG11,A.DG17,A.DG23 3 glyco-bond=-s-- groove=wn-- planarity=0.129 type=planar nts=4 GGGG A.DG6,A.DG10,A.DG18,A.DG24