Structural bases of the functional nucleic acids as the therapeutic target
Structural bases of the functional nucleic acids as the therapeutic target
批准号:
10470476
负责人:
FUJII Satoshi
金额:
$6.53万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
1998
资助国家:
日本
项目状态:
已结题
起止时间:
1998 至 2000
中文摘要
1)为了获得蛋白质和核酸的良好晶体,本实验室引进了动态光散射和晶体刻划等技术。2)用X射线衍射法测定了r(UGAGCUUCGGCUC)的单晶结构,它采用两个G-U和两个U-U的连续非规范碱基配对,并通过结构化学分析阐明了其显著的RNA双链结构。使用扭结参数清除A'形状。3)扭结参数将为核酸的不规则螺旋结构提供宽容的方面。参考NDB(Nucleic Acid Database)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,开发了几个相关程序。用户可以显示选择的结果列表,其中包含结构定义和序列属性的几个描述符。有几个因素稳定或 ...更多信息 使蛋白质的构象不稳定。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,并将其与一系列单一突变蛋白质的结构的X射线分析联合收割机相结合。4)大肠杆菌Alk-A在采用烷基化过程中被诱导,并催化切除各种烷基化碱基。Alk-A的三维结构除了可以研究其识别DNA碱基特异性的反应机制外,还可以研究其识别DNA碱基特异性的详细机制。从相关DNA糖基化酶的X射线结构和致突变研究中阐明了与双螺旋DNA复合的蛋白质的模型结构。游离酶结构在构建平台以提供具有翻转的核苷酸的弯曲和楔形DNA方面没有困难。自由结构中的螺旋-发夹-螺旋基序和插入残基L125可以在没有严重接触的情况下定位。烷基化碱被各种芳环包围,例如W218、W272、Y273和F18。色氨酸的芳族吲哚环是与带正电荷的碱基部分n-阳离子相互作用形成堆叠的良好候选物。某些疏水残基,如V128和L240,也参与底物作用。5)通过X射线结构和计算机图形学研究,阐明了MutT修复酶的底物识别和水解机理的相同模型。少
英文摘要
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
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Yuriko Yamagata: "Contribution of Hydrsgen bonds to the Contormatisnal Stabilite of Human Lysoqyme:Calorimetry and X-ray Analysis Six Tyr-Phe Mutants" Biochemistry. 37. 9355-9362 (1998)
Yuriko Yamagata:“氢键对人类溶酶体稳定性的贡献:六种 Tyr-Phe 突变体的量热法和 X 射线分析”生物化学。
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Satoshi Fujii: "Contruction of Structwal enformation Database about Nuclelic Acids" Nucleic Acids Sympoaium leries. 39. 161-162 (1998)
Satoshi Fujii:“核酸结构信息数据库的构建”核酸研讨会系列。
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Yamagata Y.Kubota M.Sumikawa Y.Funahashi J.Takano K.Fujii S.& Yutani K.: "Contribution of hydrogen bonds to the conformational stability of human lysozyme : calorimetry and X-ray analysis of six tyrosine--> phenylalanine mutants."Biochemistry. 37(26). 935
山形 Y.Kubota M.Sumikawa Y.Funahashi J.Takano K.Fujii S.
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T.Tanaka: "A'-form RNA double helix in the single aystal structure of γ(UGAGCUUCGGCUC)"Nucleic Acids Research. 27. 949-955 (1999)
T. Tanaka:“γ (UGAGCUUCGGCUC) 单一结构中的 A 型 RNA 双螺旋”《核酸研究》27. 949-955 (1999)。
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Fujii S.: "Construction of structural information database about nucleic acids"Nucleic Acids Sym.Series. 39. 161-162 (1998)
Fujii S.:“核酸结构信息数据库的构建”Nucleic Acids Sym.Series。
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Oxygen semi-permeation and electrical conducting behavior of electronic and oxide ionic conducting ceramics
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