RNA-ENZYME RECOGNITION CODES IN AMINOACYL-TRNA SYNTHESIS AND TRNA MODIFICATION

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。 遗传密码是由20种酶系统建立的，氨酰-tRNA合成酶将特定的氨基酸连接到携带与该氨基酸同源的反密码子序列的tRNA上。同样，最近有人提出，更多的tRNA修饰酶根据复杂的识别码与其RNA底物结合。我们想了解这些酶识别高度特异性tRNA的结构基础。一种研究得很好的合成酶是丙氨酰-tRNA合成酶，它最近已经被晶体学破译(Swirjo等人，Mol.细胞，2004，13(6)：829-841)。这种合成酶在受体茎中保守的G：U碱基对上识别其同源tRNA，而对tRNA反密码子不敏感。我们有大晶体的AlaRS与RNA底物复合，模仿tRNAAla的受体茎。同样，YHDG和Ykvm是两种新的酶，参与了两种不同和特定的tRNA修饰。我们有Ykvm的晶体，目前正在进行结晶试验来寻找它的tRNA复合体。

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 genetic code is established by a system of 20 enzymes, aminoacyl-tRNA synthetases, which attach specific amino acids to tRNAs carrying anti-codon sequences cognate for the amino acid. Similarly, it has been recently proposed that the more numerous tRNA modification enzymes bind to their RNA substrates according to a complex recognition code. We want to understand the structural basis of highly specific tRNA recognition by these enzymes. A well studied synthetase is alanyl-tRNA synthetase which has been recently crystallographically deciphered (Swairjo et al., Mol. Cell., 2004, 13(6):829-841). This synthetase recognizes its cognate tRNA at a conserved G:U base pair in the acceptor stem, and is indifferent toward the tRNA anticodon. We have large crystals of AlaRS complexed with an RNA substrate mimicking the acceptor stem of tRNAAla. Similarly, YHDG and Ykvm are two novel enzymes involved in two different and specific tRNA modifications. We have crystals of Ykvm, and are currently persuing its tRNA complex with crystaliization trials.