STRUCTURAL STUDIES OF AMINOACYL-TRNA SYNTHETASES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本实验旨在研究酶- rna识别和催化的结构基础。实验将包括来自大肠杆菌的谷氨酰胺- trna合成酶和半胱氨酸- trna合成酶复合物的新型配位态和修饰复合物的x射线晶体学研究。重点将放在阐明切割的立体化学途径和x射线研究上，这将支持平行蛋白质工程工作，以改变氨基酸特异性，从而提供扩展遗传密码的潜力，以包括非标准氨基酸的结合。其他实验将解决间接读出和诱导拟合构象变化在赋予tRNA合成酶特征的转移RNA和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.