6J0H

Crystal structure of Actinomycin D- d(TTGGCGAA) complex

6J0H の概要

• エントリーDOI: 10.2210/pdb6j0h/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000001
• 分子名称: DNA (5'-D(P*TP*TP*GP*GP*CP*GP*AP*A)-3'), Actinomycin D, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: mismatch dna, actinomycin d, drug-dna complex, base flip out, dna kink, dna-antibiotic complex, dna/antibiotic
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 3781.08

構造登録者

Satange, R.B.,Hou, M.H. (登録日: 2018-12-24, 公開日: 2019-07-24, 最終更新日: 2024-11-13)

主引用文献

Satange, R.,Chuang, C.Y.,Neidle, S.,Hou, M.H.
Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation.
Nucleic Acids Res., 47:8899-8912, 2019

PubMed Abstract: DNA mismatches are highly polymorphic and dynamic in nature, albeit poorly characterized structurally. We utilized the antitumour antibiotic CoII(Chro)2 (Chro = chromomycin A3) to stabilize the palindromic duplex d(TTGGCGAA) DNA with two G:G mismatches, allowing X-ray crystallography-based monitoring of mismatch polymorphism. For the first time, the unusual geometry of several G:G mismatches including syn-syn, water mediated anti-syn and syn-syn-like conformations can be simultaneously observed in the crystal structure. The G:G mismatch sites of the d(TTGGCGAA) duplex can also act as a hotspot for the formation of alternative DNA structures with a GC/GA-5' intercalation site for binding by the GC-selective intercalator actinomycin D (ActiD). Direct intercalation of two ActiD molecules to G:G mismatch sites causes DNA rearrangements, resulting in backbone distortion to form right-handed Z-DNA structures with a single-step sharp kink. Our study provides insights on intercalators-mismatch DNA interactions and a rationale for mismatch interrogation and detection via DNA intercalation.

PubMed: 31361900
DOI: 10.1093/nar/gkz653

実験手法

X-RAY DIFFRACTION (1.52 Å)