NMR INVESTIGATION OF HOOGSTEEN BASE-PAIRING IN QUINOXALINE ANTIBIOTIC DNA COMPLEXES - COMPARISON OF 2/1-ECHINOMYCIN, TRIOSTIN-A AND [N-MECYS(3),N-MECYS(7)] TANDEM COMPLEXES WITH DNA OLIGONUCLEOTIDES
NMR INVESTIGATION OF HOOGSTEEN BASE-PAIRING IN QUINOXALINE ANTIBIOTIC DNA COMPLEXES - COMPARISON OF 2/1-ECHINOMYCIN, TRIOSTIN-A AND [N-MECYS(3),N-MECYS(7)] TANDEM COMPLEXES WITH DNA OLIGONUCLEOTIDES
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DOI：
10.1093/nar/22.24.5484
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发表时间：
1994-12-11
影响因子：
14.9
通讯作者：
FEIGON, J
中科院分区：
文献类型：
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作者：
ADDESS, KJ;FEIGON, J
Hoogsteen碱基对已被证明存在于Triostin A和棘霉素与各种DNA寡核苷酸的络合物中CpG结合部位附近的碱基对中。为了了解这些不寻常的碱基对与这些喹恶啉抗生素的序列特异性的关系，用H-1核磁共振波谱研究了Triostin A与[d(ACGTACGT)](2)的YPR结合位点两侧的碱基对以及TPA特异性的[N-MeCys(3)，N-MeCys(7)]与[d(ATACGTAT)](2)的构象。在2：1 Triostin A-DNA复合体和2：1[N-MeCys(3)，N-MeCys(7)]串联DNA复合体中，末端的A.T碱基对是Hoogsteen碱基与5‘-腺嘌呤配对的syn构象。这表明TPA特异性和CPG特异性的喹恶啉抗生素都能够诱导DNA中的Hoogsteen碱基对。然而，在这两个2：1复合体中，Hoogsteen碱基配对仅限于末端碱基对。在2：1 Triostin A络合物中，内腺嘌呤是反的，而在2：1[N-MeCys(3)，N-MeCys(7)]串联DNA络合物中，内腺嘌呤是反的，与pH无关，这表明两个络合物的中心碱基对都形成Watson-Crick碱基对。这表明在TPA特异性和CpG特异性喹恶啉抗生素-DNA复合体中，Hoogsteen碱基配对的序列依赖性性质是相同的。我们计算了2triostin A-[d(ACGTACGT)](2)配合物的低分辨三维结构，并将其与其他CpG特异性喹恶啉抗生素-DNA配合物进行了比较。讨论了堆积在这些络合物中形成Hoogsteen碱基对的作用。
Hoogsteen base pairs have been demonstrated to occur in base pairs adjacent to the CpG binding sites in complexes of triostin A and echinomycin with a variety of DNA oligonucleotides. To understand the relationship of these unusual base pairs to the sequence specificity of these quinoxaline antibiotics, the conformation of the base pairs flanking the YpR binding sites of the 2:1 drug-DNA complexes of triostin A with [d(ACGTACGT)](2), and of the TpA specific [N-MeCys(3), N-MeCys(7)] TANDEM with [d(ATACGTAT)](2) have been studied by H-1 NMR spectroscopy. In both the 2:1 triostin A-DNA complex and the 2:1 [N-MeCys(3), N-MeCys(7)] TANDEM-DNA complex, the terminal A.T base pairs are Hoogsteen base paired with the 5' adenine in the syn conformation. This indicates that both TpA specific and CPG specific quinoxaline antibiotics are capable of inducing Hoogsteen base pairs in DNA. However, in both 2:1 complexes, Hoogsteen base pairing is limited to the terminal base pairs. In the 2:1 triostin A complex, the internal adenines are anti and in the 2:1 [N-MeCys(3), N-MeCys(7)] TANDEM-DNA complex, the internal guanines are anti regardless of pH, which indicates that the central base pairs of both complexes form Watson-Crick base pairs. This indicates that the sequence dependent nature of Hoogsteen base pairing is the same in TpA specific and CpG specific quinoxaline antibiotic-DNA complexes. We have calculated a low resolution three-dimensional structure of the 2triostin A-[d(ACGTACGT)](2) complex and compared it with other CpG specific quinoxaline antibiotic-DNA complexes. The role of stacking in the formation of Hoogsteen base pairs in these complexes is discussed.