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

该子项目是利用 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，不一定是研究者的机构。 遗传密码是由20种酶（氨酰-tRNA合成酶）组成的系统建立的，这些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。类似地，最近有人提出，更多的tRNA修饰酶根据复杂的识别密码与它们的RNA底物结合。我们希望了解这些酶高度特异性识别tRNA的结构基础。一种充分研究的合成酶是丙氨酰-tRNA合成酶，其最近已被晶体学破译（Swairjo等人，摩尔手机，2004，13（6）：829-841）。该合成酶在受体茎中的保守G：U碱基对处识别其同源tRNA，并且对tRNA反密码子不敏感。我们有AlaRS的大晶体与RNA底物复合，模拟tRNAAla的受体茎。类似地，YHDG和Ykvm是两种涉及两种不同且特异性的tRNA修饰的新酶。我们有Ykvm的晶体，目前正在用结晶试验来证明它的tRNA复合物。

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.