Structural basis for the binding of echinomycin to DNA duplex containing I:C mismatch

• Main Authors: Hsiang-Ti Huang, 黃香娣
• Other Authors: 侯明宏
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/ehfnhs

碩士 === 國立中興大學 === 基因體暨生物資訊學研究所 === 106 === Deoxyinosine (dI) is a naturally occurring base which can form base-pairing with all four canonical bases with different stabilities and thus may cause mutations during DNA replication process. Also, the dI may lead to altered recognition sites for DNA binding proteins. It has been shown that the presence of inosine leads to various diseases including cancers during RNA editing, however, very few information is known about the inosine acting in DNA base pairing. Furthermore, the echinomycin is a DNA binding intercalator which inserts into the DNA base pair to interfere transcription and replication. In the current study, we analyzed the effects of echinomycin binding on the structure and stability to I:C mismatched DNA. We solved the crystal structure of echinomycin binding to d(ACGICGT)/ d(ACGCCGT) duplex containing single I:C mismatch to understand the structural details of I:C mismatch recognition by echinomycin. The structural results shows that, insertion of echinomycin into DNA causes structural compression and the I:C base pair flanking bis-intercalator site shows wobble base pairing. Furthermore, the staggered quinoxaline rings of the two echinomycin that surround the I:C mismatch shows the stacking interactions within the duplex which provides the stability to overall complex .The stability of DNA is measured by using melting temperature (Tm) assay to compare differences of Tm (ΔTm) between DNAs in presence and absence of drug.Overall, the echinomycin shows specific affinity to I:C mismatch and thus can have potential applications in pharmaceuticals and DNA based nanotechnology development.