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| The EMBO Journal
(1998) 17, 2947–2960, doi:10.1093/emboj/17.10.2947 |
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| The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: the mechanism of discrimination between asparagine and aspartic acid |
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| Carmen Berthet-Colominas1, Laurence Seignovert1, Michael Härtlein1, Morten Grotli2, 3, Stephen Cusack1 and Reuben Leberman1 |
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1 European Molecular Biology Laboratory, Grenoble Outstation, BP 156X, F-38042 Grenoble, Cedex 9, France 2 European Molecular Biology Laboratory, Postfach 1022.40, D-69012 Heidelberg, Germany 3 Present address: Department of Chemistry, Carlsberg Laboratory, Gamle Carlsberg Vej 10, D-2500 Valby, Denmark Received 19 February 1998; Revised 20 March 1998; Accepted 24 March 1998. |
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| Abstract |
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| The crystal structure of Thermus thermophilus asparaginyl-tRNA synthetase has been solved by multiple isomorphous replacement and refined at 2.6 Å resolution. This is the last of the three class IIb aminoacyl-tRNA synthetase structures to be determined. As expected from primary sequence comparisons, there are remarkable similarities between the tertiary structures of asparaginyl-tRNA synthetase and aspartyl-tRNA synthetase, and most of the active site residues are identical except for three key differences. The structure at 2.65 Å of asparaginyl-tRNA synthetase complexed with a non-hydrolysable analogue of asparaginyl-adenylate permits a detailed explanation of how these three differences allow each enzyme to discriminate between their respective and very similar amino acid substrates, asparagine and aspartic acid. In addition, a structure of the complex of asparaginyl-tRNA synthetase with ATP shows exactly the same configuration of three divalent cations as previously observed in the seryl-tRNA synthetase–ATP complex, showing that this a general feature of class II synthetases. The structural similarity of asparaginyl- and aspartyl-tRNA synthetases as well as that of both enzymes to the ammonia-dependent asparagine synthetase suggests that these three enzymes have evolved relatively recently from a common ancestor. |
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| Keywords: aminoacyl-tRNA synthetase, asparagine, ATP, enzyme specificity, X-ray crystallography |
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