Unknown

Dataset Information

0

Molecular Recognition of the Hybrid-2 Human Telomeric G-Quadruplex by Epiberberine: Insights into Conversion of Telomeric G-Quadruplex Structures.


ABSTRACT: 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.

SUBMITTER: Lin C 

PROVIDER: S-EPMC6192034 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Molecular Recognition of the Hybrid-2 Human Telomeric G-Quadruplex by Epiberberine: Insights into Conversion of Telomeric G-Quadruplex Structures.

Lin Clement C   Wu Guanhui G   Wang Kaibo K   Onel Buket B   Sakai Saburo S   Shao Yong Y   Yang Danzhou D  

Angewandte Chemie (International ed. in English) 20180718 34


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<sup>+</sup> solution and converts other telome  ...[more]

Similar Datasets

| S-EPMC2556180 | biostudies-literature
| S-EPMC5516791 | biostudies-literature
| S-EPMC6765150 | biostudies-literature
| S-EPMC1976458 | biostudies-literature
| S-EPMC5435910 | biostudies-literature
| S-EPMC2817458 | biostudies-literature
| S-EPMC3977216 | biostudies-literature
| S-EPMC4038342 | biostudies-other
| S-EPMC2426654 | biostudies-literature
| S-EPMC3985656 | biostudies-literature