Disease relevance of leuS

• Molecular cloning and nucleotide sequence of the gene for Escherichia coli leucyl-tRNA synthetase [1].
• Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors [2].

High impact information on leuS

• A role for the leucyl-tRNA synthetase (EC 6.1.1.4) has been established for regulating the transport of leucine across the inner membrane of Escherichia coli by the leucine, isoleucine, valine (LIV-I) transport system [3].
• Sequence and structural similarities between the leucine-specific binding protein and leucyl-tRNA synthetase of Escherichia coli [3].
• It is possible that the yeast mitochondria have evolved to tolerate lower levels of fidelity in protein synthesis or have developed alternate mechanisms to enhance discrimination of leucine from non-cognate amino acids that can be misactivated by leucyl-tRNA synthetase [4].
• A Viable Amino Acid Editing Activity in the Leucyl-tRNA Synthetase CP1-splicing Domain Is Not Required in the Yeast Mitochondria [4].
• This phenotype has been shown to be a consequence of mutations in a nuclear gene coding for mitochondrial leucyl-tRNA synthetase [5].

Chemical compound and disease context of leuS

• The leucyl-tRNA synthetase (LeuRS) from the archaeon Pyrococcus horikoshii was overexpressed in a C-terminally truncated form in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant [6].
• Leucyl-tRNA synthetase from Escherichia coli is rapidly inactivated by 6-amino-7-chloro-5,8-dioxoquinoline (quinone), a model substance for cytostatic quinones [7].
• A conserved threonine within Escherichia coli leucyl-tRNA synthetase prevents hydrolytic editing of leucyl-tRNALeu [8].

Biological context of leuS

• 4-Azaleucine, a competitive inhibitor of leucyl-tRNA synthetase, surprisingly triggered the heat shock response [9].
• P1 transduction suggested that the most plausible gene order is leuS-mrdA-mrdB-lip [10].
• The amino acid editing active site for Escherichia coli leucyl-tRNA synthetase resides within the CP1 domain that folds discretely from the main body of the enzyme [11].
• Groups on the side chain of T252 in Escherichia coli leucyl-tRNA synthetase are important for discrimination of amino acids and cell viability [12].
• Aminoacylation complex structures of leucyl-tRNA synthetase and tRNALeu reveal two modes of discriminator-base recognition [13].

Associations of leuS with chemical compounds

• LeuRS (leucyl-tRNA synthetase) can link not only the cognate leucine but also the nearly cognate residues Ile and Met to tRNA(Leu) [14].
• Among the revertants which still contained the thermolabile leucyl-tRNA synthetase we found two classes of regulatory mutants (leuX and leu Y) which have elevated levels of this enzyme [15].
• The results support the assumption that the bacteriostatic quinone directly interferes with leucyl-tRNA synthetase in growing cells [7].
• A procedure for the large-scale isolation of leucyl-tRNA synthetase from E. cole MRE 600 is described: The enzyme was purified about 320-fold to homogeneity by precipitation with cetyl-trimethyl-ammonium bromide, two consecutive chromatographies on DEAE-cellulose and three on hydroxyapatite with an over-all yield of 4% [16].

Other interactions of leuS

• The partition behavior of isoleucyl-tRNA synthetase, leucyl-tRNA synthetase and tRNA in aqueous two-phase systems composed of the polymers poly(ethyleneglycol) and dextran was investigated [17].
• We have isolated temperature resistant revertants from temperature sensitive E. coli strains containing either a thermolabile glutaminyl-tRNA synthetase or leucyl-tRNA synthetase [15].

Analytical, diagnostic and therapeutic context of leuS

• Molecular dissection of a critical specificity determinant within the amino acid editing domain of leucyl-tRNA synthetase [18].
• Crystallization and preliminary X-ray crystallographic study of leucyl-tRNA synthetase from the archaeon Pyrococcus horikoshii [6].

References