Disease relevance of thialysine

• Thialysine-resistant mutant of Salmonella typhimurium with a lesion in the thrA gene [1].
• Thialysine can be utilized for growth by a wild type K12 strain of E. coli [2].

High impact information on thialysine

• We developed a procedure, using the toxic lysine analog S-2-aminoethyl-L-cysteine (thialysine) as the selective agent, to obtain mutant Chinese hamster lung (CHL) fibroblasts with temperature-sensitive defects affecting protein synthesis [3].
• When the conversion of radiolabeled proinsulin to insulin was inhibited by replacing arginine and lysine with the aminoacid analogs, canavanine and thialysine, the nonconverted radioactive material remained associated with Golgi-derived, coated secretory granules [4].
• Sequence signatures group SSAT with proteins that appear to have thialysine Nepsilon-acetyltransferase activity [5].
• The thialysine-resistant phenotype of the hyperactive Rhb1 mutants is suppressed by a second mutation in the effector domain [6].
• GTK also catalyzes the transamination of cystathionine, lanthionine, and thialysine to the corresponding alpha-keto acids, which cyclize to ketimines [7].

Chemical compound and disease context of thialysine

• The extent of protein lysine substitution by thialysine in E. coli cells grown in media containing the analog depends on the time interval the cells are grown in the presence of analog and on the analog concentration in the medium [8].
• Degradation of thialysine- or selenalysine-containing abnormal proteins in E. coli [9].

Biological context of thialysine

• Comparison of the thialysine-induced alterations in the cell cycle distribution between Jurkat T cells transfected with Bcl-xL gene (J/Bcl-xL) and Jurkat T cells transfected with vector (J/Neo) revealed that the apoptotic cells were mainly derived from the cells accumulated in S and G2/M phases following thialysine treatment [10].
• When Jurkat T cells were treated with thialysine (0.32-2.5 mM), apoptotic cell death along with several biochemical events such as mitochondrial cytochrome c release, caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase, and DNA fragmentation was induced in a dose- and time-dependent manner [10].
• Growth rate, cell viability and protein synthesis rate of the variant are much less affected by thialysine than the parental strain [11].
• Oxidative deamination of thialysine by snake venom L-aminoacid oxidase [12].

Anatomical context of thialysine

• Mechanism underlying cytotoxicity of thialysine, lysine analog, toward human acute leukemia Jurkat T cells [10].
• Biochemical characterization of a thialysine-resistant clone of CHO cells [13].

Associations of thialysine with other chemical compounds

• Expression of these mutants confers resistance to canavanine and thialysine, phenotypes which are similar to phenotypes exhibited by cells lacking the Tsc1/Tsc2 complex that negatively regulates Rhb1 [6].
• For comparison purposes, the same hCBS reaction was monitored via a radioactive single time point assay using 14C-(C-1)-labeled L-serine and cysteamine as substrates, counting the thialysine product, following ion exchange chromatography [14].
• Using this four-enzyme couple, we find that Km(app) = 1.2+/-0.2 mM for L-serine and 5.6+/-2.2 mM for cysteamine, with kcat = 1.3+/-0.1s(-1) for the formation of thialysine by hCBS [14].
• Degradation of thialysine- or selenalysine-containing abnormal proteins in CHO cells [15].
• Crystal structure of Homo sapiens thialysine Nepsilon-acetyltransferase (HsSSAT2) in complex with acetyl coenzyme A [16].

Gene context of thialysine

• SSAT2 should be renamed 'thialysine N(epsilon)-acetyltransferase', and may regulate this pathway [17].
• Three analogs containing thialysine, gamma- and delta-fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release [18].
• Remarkably, heterologous expression of C. elegans N-acetyltransferase D2023.4 in Escherichia coli, which does not possess a homologous gene, results in a pronounced resistance against the anti-metabolite thialysine [19].
• However, these thialysine-induced apoptotic events were significantly abrogated by an ectopic expression of Bcl-xL, which is known to block mitochondrial cytochrome c release [10].
• Thus the thialysine resistance of the mutant is mainly due to the properties of its lysyl-tRNA synthetase, which shows a greater difference of the affinities for lysine and thialysine with respect to the parental strain [13].

Analytical, diagnostic and therapeutic context of thialysine

• This was confirmed by a complementation test in which all the thialysine-resistant strains with a higher KT for lysine uptake belonged to one complementation group [20].

References