How do aminoacyl tRNA synthases recognize the right amino acid for their tRNA? What is the structural reason behind the selective recognition? I have difficulty in seeing how, for example, leucine and isoleucine can be selectively recognized by different binding pockets when they exhibit similar hydrophobicity, molecular volume etc.
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1$\begingroup$ "it seems a little bit absurd"... why? enzymes can even distinguish stereoisomers of the same molecule, let alone different molecules. $\endgroup$– user24284May 14, 2017 at 14:46
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$\begingroup$ I have rewritten the title so it reflects the question and tightened the wording . $\endgroup$– DavidMay 15, 2017 at 11:54
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1 Answer
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Aminoacyl-tRNA sythetases are highly specific to their corresponding amino acid. First, the activation site, where the amino acid binds, constitutes a complex network of intermolecular interactions. For example, threonine, catalyzed by threonyl-tRNA synthetase, is very similar to valine and serine. Valine has a methyl group instead of the hydroxy group of threonine, and serine, on the other side, has no additional methyl side group. Uniquely to threonyl-tRNA synthetase, it contains a Zn2+ ion that exhibits an interaction structure specific to threonine. Nonetheless, the threonyl-tRNA synthetase could still be mischarged with serine because the zinc ion site is not specific enough, leading to 1% mischarged tRNAs. For this purpose, aminoacyl-tRNA synthetases have a second, editing site that proofreads the charged tRNA. The editing site can recognize serine and cleave it from the tRNA.
Figure: Interaction network of the activation site of the threonyl-tRNA synthetase in A. pernix. The threonine-AMP is shown in green.
Sources:
a Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 29.2, Aminoacyl-Transfer RNA Synthetases Read the Genetic Code. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22356/
b Nagaoka, Yoshiyuki, et al. "EVOLUTION AND tRNA RECOGNITION OF THREONYL-tRNA SYNTHETASE FROM AN EXTREME THERMOPHILIC ARCHAEON, Aeropyrum pernix K1." Viva Origino 1.31 (2003), http://www.origin-life.gr.jp/3101/3101062/3101062.html