Structural highlights
Publication Abstract from PubMedG-quadruplex (G4) transitions play integral roles in regulating biological functions and can be modified by ligands. However, little is known about G4 transitions. Herein, we reveal distinct pathways of a platinum(II) compound Pt-phen converting parallel-stranded MYC G4 to a hybrid-type structure. Three NMR structures, 1:1 5'-end binding, 1:1 3'-end binding and 2:1 Pt-phen-MYC G4 complexes, were determined by NMR. We find that Pt-phen drives G4 transition at a low ratio. Under physiological 100 mM K+ conditions, a significant stable hydrogen-bonded T:T:A triad is formed at 3'-end of hybrid-type Myc1234, and consequently, Pt-phen first binds the 5'-end to form a 1:1 5'-end binding complex and then disrupts the 3' T:T:A triad and binds 3'-end to form a 2:1 complex with more Pt-phen. Remarkably, the G4 transition pathway is different in 5 mM K+ with Pt-phen first binding the 3'-end and then the 5'-end. 'Edgewise-loop and flanking/ligand/G-tetrad' sandwich structure formation and terminal T:T:A triad stabilization play decisive roles in advancing and altering transition pathways. Our work is the first to elucidate the molecular structures of G4 transitions driven by a small molecule. The ligand-driven G4 transition is a dynamic process that includes a quick G4 transition and multiple complexes formation. G-quadruplex structural transition driven by a platinum compound.,Liu W, Zhu BC, Liu LY, Xia XY, Mao ZW Nucleic Acids Res. 2022 Aug 12;50(14):7816-7828. doi: 10.1093/nar/gkac572. PMID:35766415[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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