6ZL2

Structure of a parallel c-Myc modified with 3' duplex stem-loop overhang

Summary for 6ZL2

• Entry DOI: 10.2210/pdb6zl2/pdb
• NMR Information: BMRB: 34524
• Descriptor: DNA (36-MER) (1 entity in total)
• Functional Keywords: g-quadruplex, duplex, quadruplex-duplex junction, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 11315.24

Authors

Vianney, Y.M.,Weisz, K. (deposition date: 2020-06-30, release date: 2020-10-07, Last modification date: 2024-05-15)

Primary citation

Vianney, Y.M.,Preckwinkel, P.,Mohr, S.,Weisz, K.
Quadruplex-Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands.
Chemistry, 26:16910-16922, 2020

PubMed Abstract: A parallel quadruplex derived from the Myc promoter sequence was extended by a stem-loop duplex at either its 5'- or 3'-terminus to mimic a quadruplex-duplex (Q-D) junction as a potential genomic target. High-resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q-D hybrids with a very high affinity in the order K ≈10  m irrespective of the duplex location at the quadruplex 3'- or 5'-end. NMR chemical shift perturbations identified the tetrad face of the Q-D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodynamic profiles upon binding to hybrids with either a duplex extension at the quadruplex 3'- or 5'-terminus. A large enthalpic gain and considerable hydrophobic effects are accompanied by the binding of one ligand to the 3'-Q-D junction, whereas non-hydrophobic entropic contributions favor binding with formation of a 2:1 ligand-quadruplex complex in case of the 5'-Q-D hybrid.

PubMed: 32975874
DOI: 10.1002/chem.202003540

Experimental method

SOLUTION NMR