FINDING PROTEIN SEQUENCE MOTIFS--METHODS AND APPLICATIONS

寻找蛋白质序列基序——方法和应用

• 批准号: 3759328
• 负责人: E V KOONIN
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3759328
• 关键词: binding proteins; biochemical evolution; chemical information system; computer assisted sequence analysis; computer program /software; enzyme activity; enzyme structure; glutathione transferase; information retrieval; method development; methyltransferase; oncoproteins; protein sequence; statistics /biometry; translation factor

A method for detecting conserved motifs in protein sequence databases and assessing their statistical significance was developed and implemented in the CAP (Conssitent Alignment Parser) and MoST (Motif Search Tool) programs. The MoST procedure consists of iteratively abstracting from an alignment block a weight matrix representing the conserved motif, scanning the database with this matrix, and locating new segments to add to the alignment block. The last step is based upon the statistics of score distributions for position-dependent weight matrices. This techniques was applied to the analysis of several protein classes. We showed that eukaryotic translation elongation factor EF1g contains a domain related to glutathione S-transferases (GST). Two motifs that are conserved in a vast class of GST-related proteins are defined and a possible role for the GST activity of EF1g in the assembly of protein complexes involved in translation is proposed. We found that human tumor-specific nucleolar protein P120 contains a conserved S-adenosylmethionine-binding motif, and belongs to a family of putative rRNA methyltransferases that may be involved in the control of proliferation of both eukaryotic and bacterial cells. We explored the evolution of bacterial hydrolytic dehalogenases, which are crucial for detoxification of xenobiotics. Two types of dehalogenases were shown to belong to large, distinct superfamilies of enzymes found in all organisms, each of which includes many previously uncharacterized proteins. One of these superfamilies contains transferases and oxidoreductases, in addition to hydrolases, thereby revealing an evolutionary connection between different enzyme classes. Two new superfamilies of nucleosidases were characterized, as well as an unexpected structural and evolutionary relationship between thymidine phosphorylases and anthranilate phosphoribosyltransferases. We conclude that the use of motifs, particularly in the form of position-dependent weight matrices derived from alignment blocks, for sequence database screening results in extracting of a significant amount of new information as compared to standard procedures for pairwise similarity search. A general biological conclusion is that enzyme evolution involves a complex interplay between divergence and functional convergence. In many instances, evolutionarily related enzymes catalyze different reactions, whereas enzymes of similar specificity frequently appear to have different origins.

蛋白质序列数据库中保守基序的检测方法 并评估其统计学意义， 在CAP（一致性对齐解析器）和MoST（Motif 搜索工具）程序。MoST程序包括迭代 从对准块中提取表示所述对准块的权重矩阵， 保守基序，用该矩阵扫描数据库，并定位 要添加到路线图块的新线段。最后一步是基于 位置相关权重的得分分布统计 矩阵该技术已应用于多种蛋白质的分析 班我们发现真核翻译延伸因子EF 1g 含有与谷胱甘肽S-转移酶（GST）相关的结构域。两 在大量GST相关蛋白质中保守的基序是 定义和可能的作用，GST活性的EF 1g在 组装蛋白质复合物参与翻译的建议。 我们 发现人肿瘤特异性核仁蛋白P120含有一个 保守的S-腺苷甲硫氨酸结合基序，属于一个家族 推测的rRNA甲基转移酶可能参与控制 真核细胞和细菌细胞的增殖。我们探讨了 细菌水解脱卤酶的进化，这对 异生物质的解毒。两种类型的脱卤酶被证明 属于大的，不同的超家族的酶，发现在所有 生物体，其中每一个包括许多以前没有特征的 proteins. 这些超家族之一含有转移酶， 氧化还原酶，除了水解酶，从而揭示了 不同种类酶之间的进化联系。两个新 核酸内切酶的超家族的特点，以及 胸苷之间出乎意料的结构和进化关系 磷酸化酶和邻氨基苯甲酸磷酸核糖基转移酶。我们的结论 图案的使用，特别是以位置依赖的形式， 序列数据库的来自比对块的权重矩阵 筛选结果提取了大量的新的 与成对相似性标准程序相比的信息 搜索一个普遍的生物学结论是酶的进化 涉及到分歧和功能之间复杂的相互作用， 收敛在许多情况下，进化上相关的酶催化 不同的反应，而相似特异性的酶经常 似乎有不同的起源。