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The 2 Å crystal structure of leucyl‐tRNA synthetase and its complex with a leucyl‐adenylate analogue
Author(s) -
Cusack Stephen,
Yaremchuk Anna,
Tukalo Michael
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.10.2351
Subject(s) - biology , thermus thermophilus , transfer rna , amino acyl trna synthetases , biochemistry , adenylate kinase , amino acid , aminoacylation , aminoacyl trna synthetase , proofreading , enzyme , stereochemistry , rna , chemistry , gene , escherichia coli , polymerase
Leucyl‐, isoleucyl‐ and valyl‐tRNA synthetases are closely related large monomeric class I synthetases. Each contains a homologous insertion domain of ∼200 residues, which is thought to permit them to hydrolyse (‘edit’) cognate tRNA that has been mischarged with a chemically similar but non‐cognate amino acid. We describe the first crystal structure of a leucyl‐tRNA synthetase, from the hyperthermophile Thermus thermophilus , at 2.0 Å resolution. The overall architecture is similar to that of isoleucyl‐tRNA synthetase, except that the putative editing domain is inserted at a different position in the primary structure. This feature is unique to prokaryote‐like leucyl‐tRNA synthetases, as is the presence of a novel additional flexibly inserted domain. Comparison of native enzyme and complexes with leucine and a leucyl‐ adenylate analogue shows that binding of the adenosine moiety of leucyl‐adenylate causes significant conformational changes in the active site required for amino acid activation and tight binding of the adenylate. These changes are propagated to more distant regions of the enzyme, leading to a significantly more ordered structure ready for the subsequent aminoacylation and/or editing steps.