7XDJ

Crystal structure of actinomycin D-echinomycin-d(AGCGCGT/ACGAGCT) complex

7XDJ の概要

• エントリーDOI: 10.2210/pdb7xdj/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000001 PRD_000491
• 分子名称: DNA (5'-D(P*AP*GP*CP*GP*CP*GP*T)-3'), DNA (5'-D(P*AP*CP*GP*AP*GP*CP*(BRU))-3'), DSN-ALA-N2C-MVA-DSN-ALA-NCY-MVA, ... (8 entities in total)
• 機能のキーワード: g:a mismatch, single-strand dna twist, mismatch binding antibiotic, dna, dna-antibiotic complex, dna/antibiotic
• 由来する生物種: Streptomyces; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 27277.21

構造登録者

Chien, C.M.,Satange, R.B.,Hou, M.H. (登録日: 2022-03-27, 公開日: 2022-12-14, 最終更新日: 2024-07-10)

主引用文献

Satange, R.,Kao, S.H.,Chien, C.M.,Chou, S.H.,Lin, C.C.,Neidle, S.,Hou, M.H.
Staggered intercalation of DNA duplexes with base-pair modulation by two distinct drug molecules induces asymmetric backbone twisting and structure polymorphism.
Nucleic Acids Res., 50:8867-8881, 2022

PubMed Abstract: The use of multiple drugs simultaneously targeting DNA is a promising strategy in cancer therapy for potentially overcoming single drug resistance. In support of this concept, we report that a combination of actinomycin D (ActD) and echinomycin (Echi), can interact in novel ways with native and mismatched DNA sequences, distinct from the structural effects produced by either drug alone. Changes in the former with GpC and CpG steps separated by a A:G or G:A mismatch or in a native DNA with canonical G:C and C:G base pairs, result in significant asymmetric backbone twists through staggered intercalation and base pair modulations. A wobble or Watson-Crick base pair at the two drug-binding interfaces can result in a single-stranded 'chair-shaped' DNA duplex with a straight helical axis. However, a novel sugar-edged hydrogen bonding geometry in the G:A mismatch leads to a 'curved-shaped' duplex. Two non-canonical G:C Hoogsteen base pairings produce a sharply kinked duplex in different forms and a four-way junction-like superstructure, respectively. Therefore, single base pair modulations on the two drug-binding interfaces could significantly affect global DNA structure. These structures thus provide a rationale for atypical DNA recognition via multiple DNA intercalators and a structural basis for the drugs' potential synergetic use.

PubMed: 35871296
DOI: 10.1093/nar/gkac629

実験手法

X-RAY DIFFRACTION (2.435 Å)