title: Synthetic and editing mechanisms of aminoacyl-tRNA synthetases.
abstract: Aminoacyl-tRNA synthetases (aaRS) ensure the faithful transmission of genetic information in all living cells. The 24 known aaRS families are divided into 2 structurally distinct classes (class I and class II), each featuring a catalytic domain with a common fold that binds ATP, amino acid, and the 3'-terminus of tRNA. In a common two-step reaction, each aaRS first uses the energy stored in ATP to synthesize an activated aminoacyl adenylate intermediate. In the second step, either the 2'- or 3'-hydroxyl oxygen atom of the 3'-A76 tRNA nucleotide functions as a nucleophile in synthesis of aminoacyl-tRNA. Ten of the 24 aaRS families are unable to distinguish cognate from noncognate amino acids in the synthetic reactions alone. These enzymes possess additional editing activities for hydrolysis of misactivated amino acids and misacylated tRNAs, with clearance of the latter species accomplished in spatially separate post-transfer editing domains. A distinct class of trans-acting proteins that are homologous to class II editing domains also perform hydrolytic editing of some misacylated tRNAs. Here we review essential themes in catalysis with a view toward integrating the kinetic, stereochemical, and structural mechanisms of the enzymes. Although the aaRS have now been the subject of investigation for many decades, it will be seen that a significant number of questions regarding fundamental catalytic functioning still remain unresolved.
authors.affiliation: Department of Chemistry, Portland State University, 751, Portland, OR, 97207, USA, perona@pdx.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Perona
authors.forename: Ita
authors.initials: I
authors.lastname: Gruic-Sovulj
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006801:Humans; D017393:RNA Editing; D012346:RNA, Transfer, Amino Acyl / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D012346:RNA, Transfer, Amino Acyl; D000604:Amino Acyl-tRNA Synthetases