Hydrolysis of non-cognate aminoacyl-adenylates by a class II aminoacyl-tRNA synthetase lacking an editing domain

• Published in: FEBS letters 2007-10, Vol.581 (26), p.5110-5114
• Main Authors: Gruic-Sovulj, Ita, Rokov-Plavec, Jasmina, Weygand-Durasevic, Ivana
• Format: Article
• Language: English
• Subjects: aaRS; Adenosine Monophosphate - chemistry; Aminoacyl-adenylate hydrolysis; aminoacyl-tRNA synthetase with amino acids representing Ser, Gln, Phe, Pro, Thr, Ala, Val and Leu thus for seryl-, glutaminyl-, phenylalanyl-, prolyl-, threonyl-, alanyl-, valyl- and leucyl-tRNA synthetase; Binding Sites; Cysteine - chemistry; Escherichia coli; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Hydrolysis; Kinetic proofreading; PPi; Pre-transfer editing; Protein Structure, Tertiary; pyrophosphate; RNA Editing; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Sc-, Ec- and Tt-SerRS; SerHX; Serine - analogs & derivatives; Serine - chemistry; serine hydroxamate; Serine-tRNA Ligase - chemistry; Serine-tRNA Ligase - genetics; Seryl-tRNA synthetase; seryl-tRNA synthetase from Saccharomyces cerevisiae, Escherichia coli and Thermus thermophilus, respectively; Substrate Specificity; Thermus thermophilus; Threonine - chemistry; tRNA-independent pre-transfer editing
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.09.058

Aminoacyl-tRNA synthetases, a group of enzymes catalyzing aminoacyl-tRNA formation, may possess inherent editing activity to clear mistakes arising through the selection of non-cognate amino acid. It is generally assumed that both editing substrates, non-cognate aminoacyl-adenylate and misacylated tRNA, are hydrolyzed at the same editing domain, distant from the active site. Here, we present the first example of an aminoacyl-tRNA synthetase (seryl-tRNA synthetase) that naturally lacks an editing domain, but possesses a hydrolytic activity toward non-cognate aminoacyl-adenylates. Our data reveal that tRNA-independent pre-transfer editing may proceed within the enzyme active site without shuttling the non-cognate aminoacyl-adenylate intermediate to the remote editing site.