title: The fidelity of the translation of the genetic code.
abstract: Aminoacyl-tRNA synthetases play a central role in maintaining accuracy during the translation of the genetic code. To achieve this challenging task they have to discriminate against amino acids that are very closely related not only in structure but also in chemical nature. A 'double-sieve' editing model was proposed in the late seventies to explain how two closely related amino acids may be discriminated. However, a clear understanding of this mechanism required structural information on synthetases that are faced with such a problem of amino acid discrimination. The first structural basis for the editing model came recently from the crystal structure of isoleucyl-tRNA synthetase, a class I synthetase, which has to discriminate against valine. The structure showed the presence of two catalytic sites in the same enzyme, one for activation, a coarse sieve which binds both isoleucine and valine, and another for editing, a fine sieve which binds only valine and rejects isoleucine. Another structure of the enzyme in complex with tRNA showed that the tRNA is responsible for the translocation of the misactivated amino-acid substrate from the catalytic site to the editing site. These studies were mainly focused on class I synthetases and the situation was not clear about how class II enzymes discriminate against similar amino acids. The recent structural and enzymatic studies on threonyl-tRNA synthetase, a class II enzyme, reveal how this challenging task is achieved by using a unique zinc ion in the active site as well as by employing a separate domain for specific editing activity. These studies led us to propose a model which emphasizes the mirror symmetrical approach of the two classes of enzymes and highlights that tRNA is the key player in the evolution of these class of enzymes.
authors.affiliation: Laboratoire de Biologie et Genomique Structurales, IGBMC, CNRS/INSERM/ULP, Illkirch, Strasbourg, France. sankar@igbmc.u-strasbg.fr
authors.forename: R
authors.initials: R
authors.lastname: Sankaranarayanan
authors.forename: D
authors.initials: D
authors.lastname: Moras
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D005815:Genetic Code; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017393:RNA Editing; D013914:Threonine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000604:Amino Acyl-tRNA Synthetases; D013914:Threonine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase