6ccw

Hybrid-2 form Human Telomeric G Quadruplex in Complex with Epiberberine

spinqualitylabelsall models 6ccw Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ccw is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EWV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. 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. Molecular Recognition of the Hybrid-2 Human Telomeric G-quadruplex by Epiberberine: Insights into Conversion of Telomeric G-quadruplex Structures.,Lin C, Wu G, Wang K, Onel B, Sakai S, Shao Y, Yang D Angew Chem Int Ed Engl. 2018 Jun 10. doi: 10.1002/anie.201804667. PMID:29888501 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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