Structural and Mechanistic Basis of Pre- and Posttransfer Editing by Leucyl-tRNA Synthetase

The aminoacyl-tRNA synthetases link tRNAs with their cognate amino acid. In some cases, their fidelity relies on hydrolytic editing that destroys incorrectly activated amino acids or mischarged tRNAs. We present structures of leucyl-tRNA synthetase complexed with analogs of the distinct pre- and pos...

Full description

Saved in:

Bibliographic Details
Published in:	Molecular cell Vol. 11; no. 4; pp. 951 - 963
Main Authors:	Lincecum, Tommie L., Tukalo, Michael, Yaremchuk, Anna, Mursinna, Richard S., Williams, Amy M., Sproat, Brian S., Van Den Eynde, Wendy, Link, Andreas, Van Calenbergh, Serge, Grøtli, Morten, Martinis, Susan A., Cusack, Stephen
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-04-2003
Subjects:	Adenosine - analogs & derivatives Adenosine - metabolism Amino Acids - genetics Amino Acids - metabolism Aspartic Acid - genetics Aspartic Acid - metabolism Binding Sites - genetics Leucine-tRNA Ligase - genetics Leucine-tRNA Ligase - metabolism Macromolecular Substances Molecular Conformation Protein Biosynthesis - genetics Proteins - genetics RNA Editing - genetics RNA, Transfer - genetics RNA, Transfer - metabolism
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The aminoacyl-tRNA synthetases link tRNAs with their cognate amino acid. In some cases, their fidelity relies on hydrolytic editing that destroys incorrectly activated amino acids or mischarged tRNAs. We present structures of leucyl-tRNA synthetase complexed with analogs of the distinct pre- and posttransfer editing substrates. The editing active site binds the two different substrates using a single amino acid discriminatory pocket while preserving the same mode of adenine recognition. This suggests a similar mechanism of hydrolysis for both editing substrates that depends on a key, completely conserved aspartic acid, which interacts with the α-amino group of the noncognate amino acid and positions both substrates for hydrolysis. Our results demonstrate the economy by which a single active site accommodates two distinct substrates in a proofreading process critical to the fidelity of protein synthesis.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1097-2765 1097-4164
DOI:	10.1016/S1097-2765(03)00098-4