STRUCTURAL ORIGINS OF NUCLEIC ACID SEQUENCE DISCRIMINATION BY PROTEINS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 蛋白质区分核酸序列的能力是所有生物体中基因调控和翻译控制的核心。 在这里，我们提出了详细的X射线晶体学研究的蛋白质-DNA和蛋白质-RNA复合物的细菌，人类和古细菌的起源，阐明了这一共同的主题，在各种重要的生物背景。 待研究的系统中，已经确定了组成更大组装体的组分的晶体结构，或者已经解决了天然酶/突变体，这些系统是转录调节因子Lrp、丙氨酸和半胱氨酸-tRNA合成酶（CysRS）以及DNA限制修饰酶M.HhaI和EcoRV。 较新的项目是人类CysRS，这是来自M中新型tRNA生物合成途径的两种酶，其中晶体可用，或者正在筛选蛋白质-核酸复合物以进行结晶。Mazei，以及与M. jannaschii，其可能在调节厌氧甲烷产生中起作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ability of proteins to discriminate among nucleic acid sequences is at the heart of gene regulation and translational control in all organisms. Here we propose detailed x-ray crystallographic studies of protein-DNA and protein-RNA complexes of bacterial, human, and archaeal origins which elucidate this common theme in a variety of important biological contexts. Systems to be studied for which crystal structures of components to a larger assembly have been determined, or for which native enzymes/mutants have been solved are the transcriptional regulator Lrp, the glutaminyl and cysteinyl-tRNA synthetases (CysRS), and the DNA restriction-modification enzymes M.HhaI and EcoRV. Newer projects for which crystals are available, or for which protein-nucleic acid complexes are being screened for crystallization, are the human CysRS, two enzymes from a novel tRNA biosynthetic pathway in M. mazei, and tRNA complexes with isozymes of a hydrogenase from the methanogenesis pathway of M. jannaschii, which may play a role in regulating anaerobic methane production.