This project concentrates on the aminoacyl transfer RNA synthetases. These enzymes attach amino acids to specific transfer RNAs and thereby establish the rules of the genetic code where amino acids are assigned to specific triplet nucleotide sequences (which are encoded by the transfer RNAs as anticodons). The project investigates structure-function relationships within and between the individual members of this class of enzymes, and studies the chemical and kinetic basis for the specificity of synthetase-tRNA interactions. It was recently found that a single base pair is a major determinant for the identity and recognition of a specific transfer RNA. Experiments are proposed to determine whether the binding or the catalytic step are most important for recognition, and will explore the role of this base pair in a possible conformational change in the enzyme-transfer RNA complex. For these purposes, a variety of synthetic RNA substrates will be investigated. Because a simple structural element is important for recognition, small, partial transfer RNAs will be tested as substrates for the synthetase. Other studies concentrate on isolation of a tRNA binding domain from two of the enzymes and on further delineation of structure-function motifs.
| Naganuma, Masahiro; Sekine, Shun-ichi; Chong, Yeeting Esther et al. (2014) The selective tRNA aminoacylation mechanism based on a single G•U pair. Nature 510:507-11 |
| Klipcan, Liron; Safro, Mark; Schimmel, Paul (2013) Anticodon G recognition by tRNA synthetases mimics the tRNA core. Trends Biochem Sci 38:229-32 |
| Zhou, Huihao; Sun, Litao; Yang, Xiang-Lei et al. (2013) ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Nature 494:121-4 |
| Guo, Min; Schimmel, Paul (2012) Structural analyses clarify the complex control of mistranslation by tRNA synthetases. Curr Opin Struct Biol 22:119-26 |
| Wang, Jing; Fang, Pengfei; Schimmel, Paul et al. (2012) Side chain independent recognition of aminoacyl adenylates by the Hint1 transcription suppressor. J Phys Chem B 116:6798-805 |
| Sajish, Mathew; Zhou, Quansheng; Kishi, Shuji et al. (2012) Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-? and p53 signaling. Nat Chem Biol 8:547-54 |
| Lee, Peter S; Zhang, Hui-Min; Marshall, Alan G et al. (2012) Uncovering of a short internal peptide activates a tRNA synthetase procytokine. J Biol Chem 287:20504-8 |
| Xu, Zhiwen; Wei, Zhiyi; Zhou, Jie J et al. (2012) Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing. Structure 20:1470-7 |
| Park, Min Chul; Kang, Taehee; Jin, Da et al. (2012) Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis. Proc Natl Acad Sci U S A 109:E640-7 |
| Schimmel, Paul (2011) Mistranslation and its control by tRNA synthetases. Philos Trans R Soc Lond B Biol Sci 366:2965-71 |
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