Disease relevance of leuS

• Within the domain, we have identified a crucial 20-amino-acid peptide that confers editing capacity when transplanted into the inactive Escherichia coli LeuRS editing domain [1].
• Evidence from sequence alignment and crystal structure of LeuRS from Thermus thermophilus shows that A293 was conserved as R (K) or A and is located at a small helix in the editing domain of the enzyme facing the active site [2].

High impact information on leuS

• Early fusion events between ancestral genes for the leucine-specific binding protein and leucyl-tRNA synthetase could account for the similarity and suggest that processes of aminoacylation and transport for leucine in E. coli may be performed by evolutionarily interrelated proteins [3].
• A Viable Amino Acid Editing Activity in the Leucyl-tRNA Synthetase CP1-splicing Domain Is Not Required in the Yeast Mitochondria [4].
• The kinetics of A. aeolicus LeuRS in pre-steady and steady states and cross-recognition of LeuRS and tRNA(Leu) from A. aeolicus and E. coli were studied [5].
• The molecular basis of leucine auxotrophy of quinone-treated Escherichia coli. Active site-directed modification of leucyl-tRNA synthetase by 6-amino-7-chloro-5,8-dioxoquinoline [6].
• No analogous nucleoside triphosphate was found which acts as well as ATP in binding to and supporting catalysis of leucyl-tRNA synthetase from Escherichia coli MRE 600 [7].

Biological context of leuS

• It seems that the flexibility of the first base pair affects the editing reaction of LeuRS [8].
• These recombinant plasmids were transformed or cotransformed into E. coli to produce five monomeric and five heterodimeric LeuRS mutants [9].
• Here we report the isolation and characterization of three LeuRS mutants with point mutations at this position (T252Y, T252L, and T252F) [10].
• These results suggest that the region around E292-A293 may be responsible for maintaining the proper conformation of LeuRS required for the tRNA charging activity [11].
• However, the complete genome sequence of a hyper thermophile Aquifex aeolicus suggests that the gene for leucyl-tRNA synthetases (LeuRS) is probably split into two pieces (leuS and leuS') [12].

Associations of leuS with chemical compounds

• 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].
• However, mutated LeuRS can mischarge tRNA(Leu) isoacceptors tRN or tRN with isoleucine to different extents [8].
• Leucyl-tRNA synthetase (LeuRS) relies on its editing function to correct misaminoacylation of tRNA(Leu) by isoleucine and methionine [10].
• To achieve atomic level insight into the role of T252 in LeuRS and the editing reaction of aaRSs, a series of molecular modeling studies including homology modeling and automated docking simulations were carried out [13].

Other interactions of leuS

• The argU gene helps A. aeolicus LeuRS, which contains AGA/AGG codons in exceptionally high frequency, express well in E. coli [14].

Analytical, diagnostic and therapeutic context of leuS

• Although the E292-A293-cleaved LeuRS could not catalyze aminoacylation, fluorescence titration revealed that its tRNA binding ability was almost identical to that of wild-type LeuRS [11].
• By using the genes encoding A. aeolicus and E. coli LeuRS as PCR templates, the genes encoding the alpha and beta subunits from A. aeolicus alphabeta-LeuRS and the equivalent amino- and carboxy-terminal parts of E. coli LeuRS (identified as alpha' and beta') were amplified and recombined using suitable plasmids [9].

References