Structural bases of the functional nucleic acids as the therapeutic target

1)为了获得良好的蛋白质和核酸晶体，在室内实验室中引入了动态光散射和晶体记分等技术。2)用x射线法确定了采用连续非规范碱基对（两个G-U和两个U-U）的r（UGAGCUUCGGCUC）的单晶结构，并通过结构化学分析阐明了其显著的RNA双链结构。通过使用扭结参数清除A'形式。3)扭结参数可为核酸不规则螺旋结构提供容忍度。参考NDB（核酸数据库）项目建立了包含这些扭结参数的初步数据库。利用NDB软件包和mmCIF字典，开发了几个相关的程序。用户可以显示带有结构定义和序列属性的几个描述符的选择结果列表。有几个因素稳定或…更不稳定的蛋白质构象。估计这些因素的贡献的一个有用的方法是系统地分析从量热法获得的热力学数据，并将其与一系列单突变蛋白结构的x射线分析相结合。4)在烷基化过程中诱导大肠杆菌Alk-A，并催化多种烷基化碱基的切除。Alk-A的三维结构除了反应机理外，还可以详细的回顾识别DNA碱基特异性的机制。从相关DNA糖基酶的x射线结构和诱变研究中阐明了蛋白质与双螺旋DNA络合的模型结构。自由酶结构在构建平台以提供弯曲和楔形的DNA与翻转出的核苷酸方面没有困难。螺旋-发夹-螺旋基序和自由结构中的插入残留物L125可以在没有剧烈接触的情况下定位。烷基化的碱周围有各种芳香环，如W218、W272、Y273和F18。色氨酸的芳香吲哚环是与带正电的碱基部分（n-阳离子相互作用）形成堆叠的良好候选者。一些疏水残基，如V128和L240也与底物有关。5)从x射线结构和计算机图形学研究中阐明了MutT修复酶的底物识别模型和水解机理。少

1) To obtain the good crystal of proteins and nucleic acids, several skillful techniques including the dynamic light scattering and crystal scoring have been introduced in house laboratory. 2) Single crystal structure of r(UGAGCUUCGGCUC) which adopts the successive non-canonical base pairings (two G-U's and two U-U's) has been determined by X-ray method and the notable RNA double stranded structure was elucidated from structural chemical analysis. The A' form is cleared by using kink parameters. 3) The kink parameters would provide the tolerant aspect for irregular helical structures of nucleic acid. The tentative database including these kink parameters has been constructed by referred to NDB (Nucleic Acid Database) project. Using NDB software package and mmCIF dictionary, the several related programs are developed. The user can display results list that was selected with several descriptors for the structure definition and sequence properties. There are several factors stabilizing or … More destabilizing the conformation of a protein. A useful approach for estimating the contribution of these factors is to systematically analyze the thermodynamic data obtained from calorimetry and combine this with X-ray analyses of the structures for a series of single mutant proteins. 4) Escherichia coli Alk-A is induced during adoption to alkylation and catalyzes the excision of a variety of alkylated bases. The three-dimensional structure of Alk-A can review the detailed mechanism to recognize DNA base specificity in addition to the reaction mechanism. The model structure of protein complexed with the double helical DNA is elucidated from X-ray structures of related DNA glycosylase enzymes and mutagenic studies. The free enzyme structure has no difficulty in building the platform to afford the bended and wedge DNA with the flipped out nucleotide. The helix-hairpin-helix motif and the insertion residue L125 in free structure can be located without severe contacts. The alkylated base is surrounded with a variety of aromatic rings, such as W218, W272, Y273 and F18. The aromatic indole ring of tryptophan is a good candidate for forming the stacking with the positively charged base moiety n-cation interaction). Some hydrophobic residues, such as V128 and L240, also attend to substrate 5) Same model for substrate recognition and hydrolysis mechanism of MutT, repair enzyme was elucidated from X-ray structure and computer graphical studies. Less