STRUCTURAL STUDIES OF AMINOACYL-TRNA SYNTHETASES

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。 拟议的实验研究了酶-RNA识别和催化的结构基础。实验将包括对新型连接状态的X射线结晶学研究，以及对来自大肠杆菌的谷氨酰tRNA合成酶和半胱氨基tRNA合成酶复合体的修饰复合体的研究。重点将放在阐明切割的立体化学途径和X光研究上，这些研究将支持平行的蛋白质工程工作，以改变氨基酸的特异性，从而提供扩大遗传密码以包括非标准氨基酸的可能性。其他实验将解决间接读出和诱导适合性构象变化在赋予转移RNA和tRNA合成酶所特有的氨基酸非常高的选择性方面的复杂作用。

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 proposed experiments investigate the structural basis of enzyme-RNA recognition and catalysis. Experiments will encompass Xray crystallographic studies of novel liganded states and of modified complexes for both the glutaminyl-tRNA synthetase and cysteinyl-tRNA synthetase complexes from E. coli. Emphasis will be placed on elucidating the stereochemical pathways of cleavage and on Xray studies that will support parallel protein engineering work to alter amino acid specificity, thus offering the potential to expand the genetic code to include incorporation of nonstandard amino acids. Other experiments will address the complex roles of indirect readout and induced-fit conformational change in conferring the very high selectivities for transfer RNA and for amino acid that are characteristic of tRNA synthetases.