STRUCTURAL ORIGINS OF NUCLEIC ACID SEQUENCE DISCRIMINATION BY PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 蛋白质区分核酸序列的能力是所有生物体基因调控和翻译控制的核心。在这里，我们建议对细菌、人类和古生物来源的蛋白质-DNA和蛋白质-RNA复合体进行详细的X射线结晶学研究，在各种重要的生物学背景下阐明这一共同主题。已经确定了更大组装组件的晶体结构的系统，或者已经解决了天然酶/突变体的系统是转录调节因子LRP，谷氨酰基和半胱氨基-tRNA合成酶(CysRS)，以及DNA限制修饰酶M.HhaI和EcoRV。有晶体可用或正在筛选蛋白质-核酸复合体结晶的较新项目是人类CysRS，来自玛氏分枝杆菌一种新的tRNA生物合成途径的两种酶，以及来自简氏分枝杆菌产甲烷途径的氢酶同工酶的tRNA复合体，这可能在调节厌氧甲烷产生中发挥作用。

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.