STRUCTURAL STUDIES OF AMINOACYL-TRNA SYNTHETASES

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 所提出的实验研究酶-RNA识别和催化的结构基础。 实验将包括新的配位态和修饰的复合物的X射线晶体学研究，这两种复合物都是由E.杆菌 重点将放在阐明立体化学途径的切割和X射线的研究，将支持平行的蛋白质工程工作，以改变氨基酸的特异性，从而提供了潜在的扩展遗传密码，包括纳入非标准的氨基酸。 其他实验将解决间接读出和诱导拟合构象变化的复杂作用，赋予非常高的选择性转移RNA和氨基酸的tRNA合成酶的特征。

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.