EC Number   |
General Information |
Reference |
|---|
    6.1.1.5 | evolution |
enzyme IleRS is a class I aaRS enzyme built around the conserved N-terminal Rossmann fold catalytic domain, which encloses the synthetic site. Phylogenetic analysis suggests that the ileS1 and ileS2 genes of contemporary bacteria are the descendants of genes that might have arisen by an ancient duplication event before the separation of bacteria and archaea. The accuracy of Ile-tRNAIle synthesis may be entirely ensured by the powerful post-transfer editing domain, which is absolutely conserved through evolution. The origin of discrimination against valine in the synthetic reaction is evolutionarily conserved in IleRS, overview |
745362 |
| 6.1.1.5 | evolution |
phylogenetic analysis, the origin of discrimination against valine in the synthetic reaction is evolutionarily conserved in IleRS, overview |
-, 745362 |
| 6.1.1.5 | evolution |
the enzyme belongs to the class I amino acyl-tRNA synthetases (aaRS) |
-, 744324, 745675 |
| 6.1.1.5 | malfunction |
constitutive high levels of mt isoleucyl-tRNA synthetase (mt-IleRS) are associated with reduced penetrance of the homoplasmic m.4277T>C mt-tRNAIle mutation, causing hypertrophic cardiomyopathy, which is paralleled by results in mutant transmitochondrial cybrids following overexpression of mt-IleRS. Interchangeable ability of three human mt-aaRS, namely mt-ValRS, mt-LeuRS and mt-IleRS, to suppress the mitochondrial functional defects associated with pathogenic homoplasmic mutations in mt-tRNAIle gene (MTTI). Transient overexpression of cognate mt-IleRS causes a 1.5fold increase in the viability of m.4277T>C MTTI mutant cybrids grown in galactose medium. The carboxy-terminal domain of human mt-leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with the mild mutations or with the severe m.3243A>G mutation in the mt-tRNALeu(UUR) gene. This small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNALeu(UUR) with high affinity and stability and, with lower affinity, with mt-tRNAIle |
744788 |
| 6.1.1.5 | malfunction |
mutant ileS(T233P) allows tRNAIle mischarging while retaining wild-type Ile-tRNAIle synthesis activity. The growth rate of the ileS(T233P) strain BAL4571 is not significantly different from wild-type strain BAL4574. The ileS(T233P) strain is observed to exhibit a significant defect in formation of environmentally resistant spores. The sporulation defect ranges from 3fold to 30fold and is due to a delay in activation of early sporulation genes. The loss of aminoacylation quality control in the ileS(T233P) strain results in the inability to compete with a wild-type strain under selective conditions that require sporulation. The quality control-defective IleRS mutant is defective in expressing genes activated by the master regulator of sporulation, Spo0A. Phenotype, overview. Spo0A is the first transcription factor to become active, through phosphorylation by a phosphorelay, in the sporulation regulatory cascade |
-, 746476 |
| 6.1.1.5 | malfunction |
mutations in the nuclear-encoded mitochondrial aminoacyltRNA synthetases are associated with a range of clinical phenotypes. A recessive disorder CAGSSS in three adult French-Canadian patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia is caused by a single missense mutation P909L in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl-tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level is reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 are independently identified in a patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. Phenotypes, overview |
745057 |
| 6.1.1.5 | malfunction |
under error-prone conditions Streptomyces griseus IleRS is able to rescue the growth of an Escherichia coli lacking functional IleRS, providing the first evidence that tRNA-dependent pre-transfer editing in IleRS is not essential for cell viability |
745362 |
| 6.1.1.5 | more |
a Rossmann fold peptide is loacted directly N-terminal to the strictly conserved HIGH motif. The class I IleRS Rossmann fold accommodates both synthetic and tRNA-dependent pretransfer hydrolysis pathways within the synthetic site. Residue Y59 acts as a gatekeeper of the IleRS synthetic site |
744324 |
| 6.1.1.5 | more |
in mupirocin-resistant strains, e.g. evolved strain C12 that carried several copies of ileS, the antibiotic resistance leads also to reduced growth rates, these can be restored by the organism via increased expression of the original mutant ileS gene, also improving fitness while maintaining resistance, a process of adaptation initiated by common amplifications and followed by later acquisition of rare point mutations. A point mutation in one copy relaxes selection and allows loss of defective ileS copies, overview. Model for genetic adaptation of cells to the growth limitation caused by their MupR, overview |
715118 |
| 6.1.1.5 | more |
the simultaneous presence of Ile-tRNA and Ile-AMP can cause additional possibilities to proofreading mechanisms of the enzyme, existence of an additional activation step, formation of a new isoleucyl-AMP before the isoleucyl-tRNA is freed from the enzyme. The removal of Ile-tRNA is possible without the formation of Ile-AMP if both isoleucine and ATP are bound to the E-Ile-tRNA complex, but this route covers only 11% of the total formation of Ile-tRNA |
744920 |
