Mechanism of Trna-dependent Editing in Translational Quality Control.
From: Biochemistry Program and Department of Microbiology, Ohio State University, Columbus, OH 43210, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Jan 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 1
- Pages: 72-7
- Medium: Print
- Language: English
- Citation (JAMA): Ling Jiqiang, Roy Hervé, Ibba Michael, et al. Mechanism of Trna-dependent Editing in Translational Quality Control.. Proc. Natl. Acad. Sci. U.S.A. Jan 2007;104:72-7
Abstract
Protein synthesis requires the pairing of amino acids with tRNAs catalyzed by the aminoacyl-tRNA synthetases. The synthetases are highly specific, but errors in amino acid selection are occasionally made, opening the door to inaccurate translation of the genetic code. The fidelity of protein synthesis is maintained by the editing activities of synthetases, which remove noncognate amino acids from tRNAs before they are delivered to the ribosome. Although editing has been described in numerous synthetases, the reaction mechanism is unknown. To define the mechanism of editing, phenylalanyl-tRNA synthetase was used to investigate different models for hydrolysis of the noncognate product Tyr-tRNA(Phe). Deprotonation of a water molecule by the highly conserved residue betaHis-265, as proposed for threonyl-tRNA synthetase, was excluded because replacement of this and neighboring residues had little effect on editing activity. Model building suggested that, instead of directly catalyzing hydrolysis, the role of the editing site is to discriminate and properly position noncognate substrate for nucleophilic attack by water. In agreement with this model, replacement of certain editing site residues abolished substrate specificity but only reduced the catalytic efficiency of hydrolysis 2- to 10-fold. In contrast, substitution of the 3’-OH group of tRNA(Phe) severely impaired editing and revealed an essential function for this group in hydrolysis. The phenylalanyl-tRNA synthetase editing mechanism is also applicable to threonyl-tRNA synthetase and provides a paradigm for synthetase editing.
Mesh Headings (Keywords): Binding Sites, Catalysis, Phenylalanine-tRNA Ligase, Protein Biosynthesis, RNA Editing, RNA, Transfer, Phe, Structure-Activity Relationship
Check for Full Text / PubMed Unique Identifier (PMID): 17185419
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.