7EL7

NMR solution structure of the 1:1 complex of a quadruplex-duplex hybrid MYT1L and a platinum(II) ligand L1Pt(dien)

Summary for 7EL7

• Entry DOI: 10.2210/pdb7el7/pdb
• Descriptor: G-quadruplex DNA MYT1L, Pt(diethylenetriamine)(2-(pyridin-4-ylmethyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone) (2 entities in total)
• Functional Keywords: g-quadruplex, quadruplex-duplex hybrid, complex, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 9872.46

Authors

Liu, L.-Y.,Liu, W.,Mao, Z.-W. (deposition date: 2021-04-08, release date: 2021-12-15, Last modification date: 2024-05-15)

Primary citation

Liu, L.Y.,Wang, K.N.,Liu, W.,Zeng, Y.L.,Hou, M.X.,Yang, J.,Mao, Z.W.
Spatial Matching Selectivity and Solution Structure of Organic-Metal Hybrid to Quadruplex-Duplex Hybrid.
Angew.Chem.Int.Ed.Engl., 60:20833-20839, 2021

PubMed Abstract: The sequence-dependent DNA secondary structures possess structure polymorphism. To date, studies on regulated ligands mainly focus on individual DNA secondary topologies, while lack focus on quadruplex-duplex hybrids (QDHs). Here, we design an organic-metal hybrid ligand L Pt(dien), which matches and selectively binds one type of QDHs with lateral duplex stem-loop (QLDH) with high affinity, while shows poor affinity for other QDHs and individual G4 or duplex DNA. The solution structure of QLDH MYT1L-L Pt(dien) complex was determined by NMR. The structure reveals that L Pt(dien) presents a chair-type conformation, whose large aromatic "chair surface" intercalates into the G-quadruplex-duplex interface via π-π stacking and "backrest" platinum unit interacts with duplex region through hydrogen bonding and electrostatic interactions, showing a highly matched lock-key binding mode. Our work provided guidance for spatial matching design of selectively targeting ligands to QDH structures.

PubMed: 34288320
DOI: 10.1002/anie.202106256

Experimental method

SOLUTION NMR