6XRQ

Structural descriptions of ligand interactions to DNA and RNA quadruplexes folded from the non-coding region of Pseudorabies virus

Summary for 6XRQ

• Entry DOI: 10.2210/pdb6xrq/pdb
• Descriptor: RNA (5' GP*GP*CP*UP*CP*GP*GP*CP*GP*GP*CP*GP*GP*A-3'), POTASSIUM ION, 2,7-bis[3-(morpholin-4-yl)propyl]-4,9-bis{[3-(morpholin-4-yl)propyl]amino}benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetrone, ... (4 entities in total)
• Functional Keywords: quadruplex, rna, prv
• Biological source: Pseudorabies virus Ea
• Total number of polymer chains: 2
• Total formula weight: 10872.82

Authors

Zhang, Y.S.,Parkinson, G.N.,Wei, D.G. (deposition date: 2020-07-13, release date: 2021-07-28, Last modification date: 2024-06-26)

Primary citation

Zhang, Y.,Bux, K.,Attana, F.,Wei, D.,Haider, S.,Parkinson, G.N.
Structural descriptions of ligand interactions to RNA quadruplexes folded from the non-coding region of Pseudorabies virus.
Biochimie, 2024

PubMed Abstract: To rationalise the binding of specific ligands to RNA-quadruplex we investigated several naphthalene diimide ligands that interact with the non-coding region of Pseudorabies virus (PRV). Herein we report on the x-ray structure of the naphthalene diimide ND11 with an RNA G-quadruplex putative forming sequence from rPRV. Consistent with previously observed rPRV sequence it assembles into a bimolecular RNA G-quadruplex consisting of a pair of two tetrads stacked 3' to 5'. We observe that ND11 interacts by binding on both the externally available 5' and 3' quartets. The CUC (loop 1) is structurally altered to enhance the 5' mode of interaction. These loop residues are shifted significantly to generate a new ligand binding pocket whereas the terminal A14 residue is lifted away from the RNA G-quadruplex tetrad plane to be restacked above the bound ND11 ligand NDI core. CD analysis of this family of NDI ligands shows consistency in the spectra between the different ligands in the presence of the rPRV RNA G-quadruplex motif, reflecting a common folded topology and mode of ligand interaction. FRET melt assay confirms the strong stabilising properties of the tetrasubstituted NDI compounds and the contributions length of the substituted groups have on melt temperatures.

PubMed: 38876382
DOI: 10.1016/j.biochi.2024.06.003

Experimental method

X-RAY DIFFRACTION (1.21 Å)