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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Crystal and solution structures of 7-amino-actinomycin D complexes with d(TTAGBrUT), d(TTAGTT) and d(TTTAGTTT)
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Crystal and solution structures of 7-amino-actinomycin D complexes with d(TTAGBrUT), d(TTAGTT) and d(TTTAGTTT)

机译：晶体结构和解决方案7-amino-actinomycin D复合物与D (TTAGBrUT),

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The formation of the complex of 7-amino-actinomycin D with potentially single-stranded DNA has been studied by X-ray crystallography in the solid state, by NMR in solution and by molecular modelling. The crystal structures of the complex with 5'-TTAG[(BrU)-U-5]T-3' provide interesting examples of MAD phasing in which the dispersive component of the MAD signal was almost certainly enhanced by radiation damage. The trigonal and orthorhombic crystal modifications both contain antibiotic molecules and DNA strands in the form of a 2:4 complex: in the orthorhombic form there is one such complex in the asymmetric unit, while in the trigonal structure there are four. In both structures the phenoxazone ring of the first drug intercalates between a BrU-G (analogous to T-G) wobble pair and a G-T pair where the T is part of a symmetry-related molecule. The chromophore of the second actinomycin intercalates between the BrU-G and G-BrU wobble pairs of the partially paired third and fourth strands. The base stacking also involves (A*T)*T triplets and Watson-Crick A-T pairs and leads to similar complex three-dimensional networks in both structures, with looping-out of unpaired bases. Although the available NOE constraints of a solution containing the antibiotic and d(TTTAGTTT) strands in the ratio 1:1 are insufficient to determine the structure of the complex from the NMR data alone, they are consistent with the intercalation geometry observed in the crystal structure. Molecular-dynamics (MD) trajectories starting from the 1:2 complexes observed in the crystal showed that although the thymines flanking the d(AGT) core are rather flexible and the G-T pairing is not permanently preserved, both strands remain bound to the actinomycin by strong interactions between it and the guanines between which it is sandwiched. Similar strong binding (hemi-intercalation) of the actinomycin to a single guanine was observed in the MD trajectories of a 1:1 complex. The dominant interaction is between the antibiotic and guanine, but the complexes are stabilized further by promiscuous base-pairing.
机译：的复杂的形成7-amino-actinomycin D可能单链DNA研究了x射线在固态晶体学,通过核磁共振解决方案,通过分子模拟。结构的复杂5 ' -TTAG [(BrU) -U-5]条t - 3”提供有趣的疯狂的例子逐步分散组件的信号几乎肯定是疯狂增强了辐射损伤。斜方晶系的水晶包含修改抗生素分子,DNA链的形式2:4复杂:的斜方晶系的形式就是这样一个复杂的不对称单位,而有四个三角形的结构。phenoxazone环结构的第一个药物之间插入BrU-G(类似于T-G)摆动对一对g T, T的一部分一个symmetry-related分子。第二个放线菌素之间的插入BrU-G和G-BrU摆动对部分第三和第四股。堆积还包括(A * T) * T三胞胎沃森克里克t双并导致相似复杂的三维网络结构,looping-out未配对的基地。虽然可用的一个约束包含抗生素和解决方案d (TTTAGTTT)股比例1:1确定结构的不足复杂的核磁共振数据,与夹层几何一致观察到的晶体结构。分子动力学(MD)轨迹开始1:2复合物晶体中观察到表明,尽管一侧的胸腺嘧啶d (AGT)的核心,而灵活和g t配对不是永久保存,两者兼而有之股仍然绑定到放线菌素强之间的相互作用之间的鸟嘌呤它是夹。(hemi-intercalation)放线菌素的单中可观察到鸟嘌呤1:1的轨迹复杂。抗生素和之间的交互鸟嘌呤,但复合物的进一步稳定滥交的碱基对。

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