Chapter category: RNA

Phenylalanyl-tRNA Synthetases

This chapter appears in the following book:

The Aminoacyl-tRNA Synthetases

Edited by: Michael Ibba
ISBN: 1-58706-189-9
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Chapter authors:
Mark Safro, Nina Moor and Olga Lavrik

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Phenylalanyl-tRNA synthetase (PheRS) is shown to be among the most complex of the aminoacyl-tRNA synthetases (aaRSs) with the tetrameric subunit organization of cytoplasmic PheRS markedly conserved during evolution. The structure of Thermus thermophilus PheRS complexed with tRNAPhe has explained the functional necessity for PheRS to be (αβ)2 heterodimeric. The divalent cation detected at the interface of the α- and β-subunits is important for the enzyme activity and αβ heterodimer stability. The heterodimeric structure is not a prerequisite of the phenylalanylation activity: monomeric mitochondrial PheRSs are also active. Structurally, the enzyme belongs to class II, as its catalytic domain is built around an antiparallel β sheet, but functionally it resembles class I, aminoacylating the 2' OH group of the tRNA terminal ribose. The major determinants of tRNAPhe specificity are three nucleotides of the anticodon, directly recognized by the RNP (the subclass IIc specific) domain of the β-subunit. Multiple minor elements scattered over tRNAPhe contribute to the recognition of its general shape, mostly through backbone interactions with the N-terminal coiled-coil domain of the α-subunit, and to mutual steric adaptation of the tRNA and PheRS. The proper positioning of the tRNAPhe acceptor end corresponding to the structure of the productive complex is promoted only in the presence of phenylalanyl-adenylate; the base-specific contacts of the terminal adenosine dictate the conformational rearrangement of the tRNA in aminoacylation reaction. Specific recognition of the phenylalanine substrate is achieved by interactions of the phenyl ring with two neighbouring phenylalanine residues in the protein. No metal ions have been observed within the active site of PheRS complexed with phenylalanyl-adenylate. The peculiarity of the aminoacylation site in this system is governed by stepwise adjustment of all the reactants and intermediates in the active site. The structural fragments of PheRS reveal multiple similarities to those of different DNA/RNA binding proteins, suggesting a puzzling evolution of the enzyme and existence of a range of functions additional to the main activity.

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Chapter category: RNA

Phenylalanyl-tRNA Synthetases

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