5YTZ

Crystal structure of echinomycin-d(ACGTCGT)2 complex

5YTZ の概要

• エントリーDOI: 10.2210/pdb5ytz/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000491
• 分子名称: DNA (5'-D(P*AP*CP*GP*TP*CP*GP*(UD))-3'), Echinomycin, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: echinomycin, dna intercalator, antibiotic, echinomycin-dna complex, mismatched base pairs, t-t mismatch, pyrimidine-pyrimidine base pairing, dna mismatch repair (mmr), non-canonical duplex structure, antibiotic-dna complex, antibiotic/dna
• 由来する生物種: Streptomyces echinatus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 6820.17

構造登録者

Hou, M.H.,Wu, P.C.,Kao, Y.F. (登録日: 2017-11-20, 公開日: 2018-05-23, 最終更新日: 2023-11-22)

主引用文献

Wu, P.C.,Tzeng, S.L.,Chang, C.K.,Kao, Y.F.,Waring, M.J.,Hou, M.H.
Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex
Nucleic Acids Res., 46:7396-7404, 2018

PubMed Abstract: Small-molecule compounds that target mismatched base pairs in DNA offer a novel prospective for cancer diagnosis and therapy. The potent anticancer antibiotic echinomycin functions by intercalating into DNA at CpG sites. Surprisingly, we found that the drug strongly prefers to bind to consecutive CpG steps separated by a single T:T mismatch. The preference appears to result from enhanced cooperativity associated with the binding of the second echinomycin molecule. Crystallographic studies reveal that this preference originates from the staggered quinoxaline rings of the two neighboring antibiotic molecules that surround the T:T mismatch forming continuous stacking interactions within the duplex. These and other associated changes in DNA conformation allow the formation of a minor groove pocket for tight binding of the second echinomycin molecule. We also show that echinomycin displays enhanced cytotoxicity against mismatch repair-deficient cell lines, raising the possibility of repurposing the drug for detection and treatment of mismatch repair-deficient cancers.

PubMed: 29741655
DOI: 10.1093/nar/gky345

実験手法

X-RAY DIFFRACTION (1.55 Å)