7msv

Solution Structure of Berberine Bound to a dGMP Fill-in G-Quadruplex in the PDGFR-b Promoter

spinqualitylabelsall models 7msv, 10 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7msv is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BER, DGP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The G-quadruplexes (G4s) formed in the PDGFR-beta gene promoter are transcriptional modulators and amenable to small-molecule targeting. Berberine (BER), a clinically important natural isoquinoline alkaloid, has gained increasing attention due to its potential as anticancer drug. We previously showed that the PDGFR-beta gene promoter forms a unique vacancy G4 (vG4) that can be filled in and stabilized by guanine metabolites, such as dGMP. Herein, we report the high-resolution NMR structure of a ternary complex of berberine bound to the dGMP-fill-in PDGFR-beta vG4 in potassium solution. This is the first small-molecule complex structure of a fill-in vG4. This ternary complex has a 2:1:1 binding stoichiometry with a berberine molecule bound at each the 5'- and 3'-end of the 5'-dGMP-fill-in PDGFR-beta vG4. Each berberine recruits the adjacent adenine residue from the 5'- or 3'-flanking sequence to form a "quasi-triad plane" that covers the external G-tetrad of the fill-in vG4, respectively. Significantly, berberine covers and stabilizes the fill-in dGMP. The binding of berberine involves both pi-stacking and electrostatic interactions, and the fill-in dGMP is covered and well-protected by berberine. The NMR structure can guide rational design of berberine analogues that target the PDGFR-beta vG4 or dGMP-fill-in vG4. Moreover, our structure provides a molecular basis for designing small-molecule guanine conjugates to target vG4s. Solution Structure of Ternary Complex of Berberine Bound to a dGMP-Fill-In Vacancy G-Quadruplex Formed in the PDGFR-beta Promoter.,Wang KB, Dickerhoff J, Yang D J Am Chem Soc. 2021 Oct 13;143(40):16549-16555. doi: 10.1021/jacs.1c06200. Epub, 2021 Sep 29. PMID:34586799 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA