8TAA

Right-left hybrid parallel G-quadruplex in complex with N-methyl mesoporphyrin

8TAA の概要

• エントリーDOI: 10.2210/pdb8taa/pdb
• 分子名称: DNA (25-MER), SPERMINE (FULLY PROTONATED FORM), (4S)-2-METHYL-2,4-PENTANEDIOL, ... (6 entities in total)
• 機能のキーワード: g-quadruplex, right-left-handed, parallel, nmm, dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8991.64

構造登録者

Seth, P.C.,Yatsunyk, L.A. (登録日: 2023-06-27, 公開日: 2024-07-03, 最終更新日: 2025-02-05)

主引用文献

Seth, P.,Xing, E.,Hendrickson, A.D.,Li, K.,Monsen, R.,Chaires, J.B.,Neidle, S.,Yatsunyk, L.A.
Interaction of N-methylmesoporphyrin IX with a hybrid left-/right-handed G-quadruplex motif from the promoter of the SLC2A1 gene.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands is underexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5'- and 3'-direction from its genomic context. We also investigate whether this sequence interacts with a well-established G4 binder, N-methylmesoporphyrin IX (NMM). We employed biophysical and X-ray structural studies to address these questions. Our results indicate that the sequence d[G(TGG)3TGA(TGG)4] (termed here as SLC) adopts a two-subunit, four-tetrad hybrid left-/right-handed G4 (LH/RHG4) topology. Addition of 5'-G or 5'-GG abolishes the left-handed fold in one subunit, while the addition of 3'-C or 3'-CA maintains the original fold. X-ray crystal structure analyses show that SLC maintains the same hybrid LH/RHG4 fold in the solid state and that NMM stacks onto the right-handed subunit of SLC. NMM binds to SLC with a 1:1 stoichiometry and a moderate-to-tight binding constant of 15 μM-1. This work deepens our understanding of LHG4 structures and their binding with traditional G4 ligands.

PubMed: 39704129
DOI: 10.1093/nar/gkae1208

実験手法

X-RAY DIFFRACTION (1.45 Å)