X-RAY STUDIES ON NUCLEIC ACID CONSTITUENTS

核酸成分的 X 射线研究

• 批准号: 3269098
• 负责人: MUTTAIYA SUNDARALINGAM
• 金额: $ 20.78万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269098
• 关键词: DNA; DNA binding protein; X ray crystallography; antineoplastic antibiotics; antineoplastics; chemical models; conformation; flavins; gene expression; metal complex; nuclear magnetic resonance spectroscopy; nucleic acid chemical synthesis; nucleic acid sequence; nucleic acid structure; nucleobase; oligonucleotides; polynucleotides; protein structure; spermine; stereochemistry

DESCRIPTION: (Adapted from applicant's abstract) The main focus of this research is to continue the single crystal X-ray diffraction studies of DNA oligomers of defined sequence. The work is aimed at providing a better understanding of the global/local conformations of DNA as regulated by base sequence. Studies of DNA octamers will be continued to look for other examples of DNA sequences the bind spermine, an ubiquitous oligocation in cells. The determination of the structure of the first A-DNA dodecamer in this laboratory provided precise values for the geometry of A-DNA, particularly the major groove dimension, which was found to be markedly narrower than in the shorter A-DNA oligomers. More dodecamers will be studied to provide better estimates of the major groove width and explore the influence of sequence changes on the A-DNA conformational parameters. Besides the A-DNA oligomers, B-DNA dodecamers, which have an inverted sequence at the core, viz with the T's preceding the A's, will be studied. These are of interest because, unlike the AxTx sequences, the TxAx sequences do not display anomalous gel migration properties. Crystals and data on at least one structure in each class (A-octamer, A-dodecamer, B-dodecamer) are already available. Whenever possible, complexes of drugs, such as netropsin, with the B-DNA will be investigated. Different crystal forms of the same sequence will be studied whenever available to compare sequence effects and crystal environmental effects on DNA conformation. The role of solvents in nucleic acids will be investigated by carefully examining the interaction of the waters of hydration with individual bases, sugars and phosphates, as well as its distribution in the grooves, along the sugar-phosphate backbone and its participation in intermolecular interactions. These X-ray crystallographic studies will be carried out using the highest resolution data. The long term goals of this project are to determine the molecular structures of DNAs with longer sequences (more than 12 nucleotides), oligomers with adjacent stretches having the potential for forming A- and B-DNA and B- and Z-DNA, to study the geometries of the geometries of the A-B and B-Z junctions. Longer DNA oligomers having sequential A-tracts will also be studied to obtain a better picture of DNA bending. This investigation will provide important details on the molecular geometries and conformations of DNAs which will be of fundamental importance in the understanding of the molecular basis of gene regulation and expression.

描述：（改编自申请人的摘要）本文的主要焦点 研究将继续DNA的单晶X射线衍射研究 具有确定序列的寡聚物。 这项工作旨在提供更好的 了解碱基调节的 DNA 全局/局部构象 顺序。 DNA八聚体的研究将继续寻找其他 结合精胺的 DNA 序列示例，精胺是一种普遍存在的寡聚阳离子 细胞。 第一个A-DNA十二聚体结构的测定 该实验室提供了 A-DNA 几何形状的精确值， 特别是主凹槽尺寸，发现明显 比较短的 A-DNA 寡聚体更窄。 更多十二相机将会 研究以更好地估计主凹槽宽度并探索 序列变化对A-DNA构象参数的影响。 除了 A-DNA 寡聚体之外，B-DNA 十二聚体也具有倒置的 将研究核心序列，即 T 在 A 之前。 这些很有趣，因为与 AxTx 序列不同，TxAx 序列不显示异常凝胶迁移特性。 晶体和 每个类别中至少一个结构的数据（A-八聚体、A-十二聚体、 B-dodecamer）已经可用。 只要有可能，药物复合物， 例如 netropsin，将与 B-DNA 一起进行研究。 异晶 只要可以比较，就会研究相同序列的形式 序列效应和晶体环境对DNA构象的影响。 将仔细研究溶剂在核酸中的作用 检查水合水与各个碱基的相互作用， 糖和磷酸盐，以及它们在凹槽中的分布，沿着 糖-磷酸骨架及其参与分子间 互动。 这些X射线晶体学研究将进行 使用最高分辨率的数据。 该项目的长期目标是 确定具有较长序列的 DNA 的分子结构（更多 超过12个核苷酸），具有相邻延伸的寡聚物具有 形成 A- 和 B-DNA 以及 B- 和 Z-DNA 的潜力，以研究 A-B 和 B-Z 交叉点的几何形状。 更长的DNA 还将研究具有连续 A-tracts 的寡聚物以获得 DNA 弯曲的更好图像。 这项调查将提供重要 有关 DNA 分子几何形状和构象的详细信息， 对于理解分子基础具有重要意义 基因调控和表达。