5YTY

Crystal structure of echinomycin-d(ACGACGT/ACGTCGT) complex

Summary for 5YTY

• Entry DOI: 10.2210/pdb5yty/pdb
• Related PRD ID: PRD_000491
• Descriptor: DNA (5'-D(P*AP*CP*GP*AP*CP*GP*T)-3'), DNA (5'-D(P*AP*CP*GP*TP*CP*GP*T)-3'), echinomycin, ... (7 entities in total)
• Functional Keywords: dna intercalator, echinomycin-dna complex, watson-crick, heptamer duplex, antibiotic-dna complex, antibiotic/dna
• Biological source: Streptomyces echinatus; More
• Total number of polymer chains: 4
• Total formula weight: 6654.02

Authors

Hou, M.H.,Wu, P.C.,Kao, Y.F. (deposition date: 2017-11-20, release date: 2018-05-23, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.58 Å)