5yty

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

spinqualitylabelsall models 5yty, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5yty is a 4 chain structure with sequence from Streptomyces echinatus and Unidentified. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.58Å Ligands: DSN, MG, MN, MVA, N2C, NCY, QUI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex.,Wu PC, Tzeng SL, Chang CK, Kao YF, Waring MJ, Hou MH Nucleic Acids Res. 2018 May 8. pii: 4993785. doi: 10.1093/nar/gky345. PMID:29741655 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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