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结合动力学揭示的诺加霉素在DNA中的不同结合位点的证据。

Evidence of different binding sites for nogalamycin in DNA revealed by association kinetics.

作者信息

Fox K R, Waring M J

出版信息

Biochim Biophys Acta. 1984 Nov 28;802(2):162-8. doi: 10.1016/0304-4165(84)90157-0.

DOI:10.1016/0304-4165(84)90157-0
PMID:6498212
Abstract

The kinetics of association between nogalamycin and DNA have been measured by stopped-flow spectrometry. With a naturally occurring DNA (calf thymus) the reaction profile requires not less than three exponentials for its complete description. By contrast, binding to poly(dA-dT) is fully described by two exponentials which correspond to the two faster components seen with the natural DNA, whereas binding to poly(dG-dC) is a single exponential process whose time constant is about the same as the slowest component measured with calf thymus DNA. In all cases the amplitude of each component in the decay varies considerably with polynucleotide concentration. The results are consistent with a model in which the antibiotic is only able to bind directly to regions of the DNA which are transiently perturbed, probably non-basepaired. As a result, the antibiotic interacts much faster with AT-rich rather than GC-rich DNA sequences, which may provide a basis for its apparent sequence selectivity.

摘要

通过停流光谱法测定了诺加霉素与DNA之间的结合动力学。对于天然存在的DNA(小牛胸腺DNA),反应曲线需要不少于三个指数来完整描述。相比之下,与聚(dA-dT)的结合完全由两个指数描述,这两个指数对应于天然DNA中观察到的两个较快的组分,而与聚(dG-dC)的结合是一个单指数过程,其时间常数与用小牛胸腺DNA测量的最慢组分大致相同。在所有情况下,衰变中每个组分的幅度随多核苷酸浓度有很大变化。这些结果与一个模型一致,在该模型中,抗生素只能直接结合到DNA中瞬时受到扰动的区域,可能是非碱基配对的区域。因此,抗生素与富含AT的DNA序列的相互作用比与富含GC的DNA序列快得多,这可能为其明显的序列选择性提供了基础。

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Evidence of different binding sites for nogalamycin in DNA revealed by association kinetics.结合动力学揭示的诺加霉素在DNA中的不同结合位点的证据。
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引用本文的文献

1
Transferring the purine 2-amino group from guanines to adenines in DNA changes the sequence-specific binding of antibiotics.将DNA中鸟嘌呤的嘌呤2-氨基转移至腺嘌呤会改变抗生素的序列特异性结合。
Nucleic Acids Res. 1995 Mar 25;23(6):885-92. doi: 10.1093/nar/23.6.885.
2
DNA structure and perturbation by drug binding.DNA结构与药物结合引起的扰动。
Biochem J. 1987 Apr 1;243(1):1-13. doi: 10.1042/bj2430001.
3
Antibiotics which can alter the rotational orientation of nucleosome core DNA.能够改变核小体核心DNA旋转方向的抗生素。
Nucleic Acids Res. 1986 Nov 25;14(22):8735-54. doi: 10.1093/nar/14.22.8735.
4
Structure of nogalamycin bound to a DNA hexamer.与DNA六聚体结合的诺加霉素的结构。
Proc Natl Acad Sci U S A. 1990 Mar;87(6):2225-9. doi: 10.1073/pnas.87.6.2225.
5
Anthracycline antibiotic arugomycin binds in both grooves of the DNA helix simultaneously: an NMR and molecular modelling study.蒽环类抗生素阿柔比星同时结合于DNA螺旋的两条沟中:一项核磁共振和分子模拟研究。
Nucleic Acids Res. 1991 Jun 11;19(11):2897-906. doi: 10.1093/nar/19.11.2897.