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Science 13 August 1999:
Vol. 285. no. 5430, pp. 1074 - 1077
DOI: 10.1126/science.285.5430.1074
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Reports

Insights into Editing from an Ile-tRNA Synthetase Structure with tRNAIle and Mupirocin

Laura F. Silvian, 13* Jimin Wang, 1 Thomas A. Steitz 123

Isoleucyl-transfer RNA (tRNA) synthetase (IleRS) joins Ile to tRNAIle at its synthetic active site and hydrolyzes incorrectly acylated amino acids at its editing active site. The 2.2 angstrom resolution crystal structure of Staphylococcus aureus IleRS complexed with tRNAIle and Mupirocin shows the acceptor strand of the tRNAIle in the continuously stacked, A-form conformation with the 3' terminal nucleotide in the editing active site. To position the 3' terminus in the synthetic active site, the acceptor strand must adopt the hairpinned conformation seen in tRNAGln complexed with its synthetase. The amino acid editing activity of the IleRS may result from the incorrect products shuttling between the synthetic and editing active sites, which is reminiscent of the editing mechanism of DNA polymerases.

1 Departments of Molecular Biophysics and Biochemistry and
2 Chemistry, Yale University, and
3 Howard Hughes Medical Institute, New Haven, CT 06520-8114, USA.
*   Present address: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

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