MOLECULAR NOVELTY IN SEQUENCES OF BACTERIA AND MODEL ORGANISMS

细菌和模型生物序列中的分子新颖性

• 批准号: 6162793
• 负责人: J C WOOTTON
• 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/6162793
• 关键词: Archaea; DNA binding protein; Escherichia coli; bacterial DNA; bacterial proteins; biochemical evolution; computer assisted sequence analysis; computer data analysis; computer system design /evaluation; microorganism metabolism; photosynthetic bacteria; protein sequence; protein structure function

Protein sequences deduced from gene sequences of diverse bacteria land archaebacteria, and also, increasingly, from eukaryotic model organisms, are yielding a wealth of new knowledge on protein functions, interactions and evolution. Novel findings, that emerged initially from computational analysis of sequences and sequence databases, have been studied in collaboration with experimental laboratories by concerted methods including directed mutagenesis and spectroscopic/enzymological analyses. Computational strategies are being developed to recognize some of the functional amino acid sequence patterns involved, many of which are subtle and variable. A. Proteins and protein complexes involved in DNA binding, mutagenesis and repair. For patterns of wall-established DNA binding regions, new methods for evaluation of pattern discriminators are being developed and applied to more novel patterns. Low- complexity sequences are frequent in components of multisubunit DNA-binding complexes and require analysis and filtering before database searches. Methods of automated local multiple alignment by iterative sampling are included and evaluated based on test sets of various types of DNA-binding motifs. B. Sequence families in complex bacteria including pathogens. The rapidly growing body of new sequences from pathogenic bacteria, and widely diverse prokaryotes such as multicellular or differentiating bacteria, cyanobacteria and archaebacteria, were investigated by a range of computational analyses. More than 50 percent of the classifiable protein sequences did not have counterparts in E. coli and other well-studied bacteria, and many of these had eukaryotic homologs. Examples of low-complexity segments and multiple repeats are emerging with increasing frequency, especially in proteins involved in surface interactions, for example with the immune system, many of which evolve rapidly. In other cases, novel chemical and metabolic functions have been found. Genome sequences and protein structural studies from matabolically and morphogenetically diverse bacteria and other model organisms continue to provide a rich and cost-effective source of new discoveries on the molecular functions and evolution of proteins including aspects related to human diseases.

从多种基因序列推导出的蛋白质序列 细菌登陆古细菌，并且也越来越多地来自 真核模型生物，正在产生大量新的 有关蛋白质功能、相互作用和进化的知识。 最初来自计算的新颖发现 序列和序列数据库的分析， 与实验实验室合作研究 协调一致的方法，包括定向诱变和 光谱/酶学分析。 计算型 正在制定战略以认识到一些 涉及的功能性氨基酸序列模式，许多 这是微妙和可变的。 A. 参与 DNA 结合的蛋白质和蛋白质复合物， 诱变和修复。 对于墙体图案 DNA 结合区域，模式评估的新方法 鉴别器正在被开发并应用于更多 新颖的图案。 低复杂度序列常见于 多亚基 DNA 结合复合物的成分和 需要在数据库搜索之前进行分析和过滤。 通过迭代自动局部多重比对的方法 包括抽样并根据测试集进行评估 各种类型的 DNA 结合基序。 B. 复杂细菌的序列家族，包括 病原体。 快速增长的新序列体 病原菌和广泛多样的原核生物，例如 多细胞或分化细菌、蓝细菌 和古细菌，通过一系列的研究 计算分析。 超过50%的 可分类的蛋白质序列在 大肠杆菌和其他经过充分研究的细菌，其中许多 具有真核同源物。 低复杂度的例子 随着越来越多的片段和多重重复不断出现 频率，尤其是涉及表面的蛋白质 相互作用，例如与免疫系统的相互作用，许多 其发展迅速。 在其他情况下，新型化学物质和 已发现代谢功能。 基因组序列和 从代谢和蛋白质结构研究 形态发生多样化的细菌和其他模型 有机体继续提供丰富且具有成本效益的 分子功能新发现的来源 蛋白质的进化，包括与人类相关的方面 疾病。