the crucial role of divalent metal ions in the dna-acting efficacy and inhibition of the transcription of dimeric chromomycin a3二价金属离子的至关重要的作用在dna-acting疗效和抑制转录的二聚的色霉素a3.pdfVIP

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the crucial role of divalent metal ions in the dna-acting efficacy and inhibition of the transcription of dimeric chromomycin a3二价金属离子的至关重要的作用在dna-acting疗效和抑制转录的二聚的色霉素a3.pdf

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the crucial role of divalent metal ions in the dna-acting efficacy and inhibition of the transcription of dimeric chromomycin a3二价金属离子的至关重要的作用在dna-acting疗效和抑制转录的二聚的色霉素a3

The Crucial Role of Divalent Metal Ions in the DNA- Acting Efficacy and Inhibition of the Transcription of Dimeric Chromomycin A3 1 2 1,3 1,3,4 Chun-Wei Hsu , Show-Mei Chuang , Wen-Ling Wu , Ming-Hon Hou * 1 Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan, 2 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, 3 Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, 4 Department of Life Science, National Chung Hsing University, Taichung, Taiwan Abstract Chromomycin A3 (Chro) is capable of forming a stable dimeric complex via chelation with Ni(II), Fe(II) and Co(II). According to the circular dichroism study, the dimer conformations are significantly different among the Fe(II)-, Co(II)-, and Ni(II)- containing dimeric Chro complexes; however, the dimer conformations were preserved at high temperatures. Furthermore, we conducted a systematic study to determine the effects of these divalent metal ions on the DNA-acting efficacy of dimeric Chro, including its DNA-binding affinity, DNA stabilization capacity, DNA cleavage activity, and the inhibition of transcription both in vitro and within cells. Kinetic analyses using surface plasmon resonance (SPR) showed that NiII(Chro)2 exhibited the highest Ka with a value of 1.26 6107 M21, which is approximately 1.6- and 3.7-fold higher than the Ka values obtained for CoII II (Chro) and Fe (Chro) , respectively. The T and DG values for the DNA duplex increased after the addition of drug 2 2 m complexes in the following order: NiII