L-Arginine recognition by yeast arginyl-tRNA synthetase

The crystal structure of arginyl‐tRNA synthetase (ArgRS) from Saccharomyces cerevisiae, a class I aminoacyl‐tRNA synthetase (aaRS), with L‐Arginine bound to the active site has been solved at 2.75 Å resolution and refined to a crystallographic R‐factor of 19.7%. ArgRS is composed predominantly of α‐helices and can be divided into five domains, including the class I‐specific active site. The N‐terminal domain shows striking similarity to some completely unrelated proteins and defines a module which should participate in specific tRNA recognition. The C‐terminal domain, which is the putative anticodon‐binding module, displays an all‐α‐helix fold highly similar to that of Escherichia coli methionyl‐tRNA synthetase. While ArgRS requires tRNAArg for the first step of the aminoacylation reaction, the results show that its presence is not a prerequisite for L‐Arginine binding. All H‐bond‐forming capability of L‐Arginine is used by the protein for the specific recognition. The guanidinium group forms two salt bridge interactions with two acidic residues, and one H‐bond with a tyrosine residue; these three residues are strictly conserved in all ArgRS sequences. This tyrosine is also conserved in other class I aaRS active sites but plays several functional roles. The ArgRS structure allows the definition of a new framework for sequence alignments and subclass definition in class I aaRSs.