Looped out and perpendicular: Deformation of Watson-Crick base pair associated with actinomycin D binding
Looped out and perpendicular: Deformation of Watson-Crick base pair associated with actinomycin D binding
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DOI：
10.1073/pnas.102580399
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发表时间：
2002-05-14
影响因子：
11.1
通讯作者：
Chen, FM
中科院分区：
文献类型：
--
作者：
Chou, SH;Chin, KH;Chen, FM
许多抗癌药物直接与DNA相互作用以发挥其生物学功能。迄今为止，所有非共价的嵌入药物都通过将它们的发色团插入碱基步骤中与DNA相互作用，以形成伸长和解绕的双链体结构，而不破坏侧翼碱基对。以放线菌素D（ActD）-5 '-GXC/CYG-5'复合物为例，我们发现了一种相当不寻常的嵌入式药物相互作用模式：中心Watson-Crick X/Y碱基对被ActD发色团环出并置换。环出碱基不是无序的，而是与碱基/发色团垂直相互作用，并与DNA形成特异性H键。这种复杂的结构为配体如何与DNA相互作用提供了有趣的见解，并扩大了序列特异性DNA识别的库。
Many anticancer drugs interact directly with DNA to exert their biological functions. To date, all noncovalent, intercalating drugs interact with DNA exclusively by inserting their chromophores into base steps to form elongated and unwound duplex structures without disrupting the flanking base pairs. By using actinomycin D (ActD)-5'-GXC/CYG-5' complexes as examples, we have found a rather unusual interaction mode for the intercalated drug; the central Watson-Crick X/Y base pairs are looped out and displaced by the ActD chromophore. The looped-out bases are not disordered but interact perpendicularly with the base/chromophore and form specific H bonds with DNA. Such a complex structure provides intriguing insights into how ligand interacts with DNA and enlarges the repertoires for sequence-specific DNA recognition.