Disease relevance of Thiosine

• In vivo inhibition by S-(2-aminoethyl)-L-cysteine was investigated by replacing the endogenous LysRS2 of Bacillus subtilis with LysRS1 from the Lyme disease pathogen Borrelia burgdorferi [1].
• A mutant of Salmonella typhimurium was selected for its spontaneous resistance to the lysine analog, thialysine (S-2-aminoethyl cysteine) [2].
• Decreasing the basicity of the active site base, Lys-258, of Escherichia coli aspartate aminotransferase by replacement with gamma-thialysine [3].
• S-2-Aminoethyl cysteine (AEC) reduced both growth rate and final growth level of Serratia marcescens Sr41 [4].
• The Corynebacterium glutamicum aecD gene encodes a C-S lyase with alpha, beta-elimination activity that degrades aminoethylcysteine [5].

High impact information on Thiosine

• Thus, manipulation of the amino acid binding site only allowed up to a 4-fold improvement in S-(2-aminoethyl)-L-cysteine discrimination [6].
• This is in contrast to the highly effective discrimination against S-(2-aminoethyl)-L-cysteine by class I LysRS and correlates with the fundamentally different roles of conserved aromatic residues in the two LysRS active sites [6].
• This observation suggested a revised catalytic mechanism in which lysine 267 facilitates hydride transfer from reduced coenzyme by polarizing the carbonyl group of HMG-CoA and subsequently of bound mevaldehyde, an inference supported by mutagenesis of lysine 267 to aminoethylcysteine [7].
• Alkylation of the K258C mutant of the wild-type aspartate aminotransferase (AATase) with bromoethylamine to give gamma-thialysine 258 was complicated by partial reaction with the five native cysteines [Planas, A., & Kirsch, J. F. (1991) Biochemistry 30, 8268-8276] [3].
• In contrast with other inhibitors of the NADH dehydrogenase of the respiratory chain, the decarboxylated dimer of aminoethylcysteine ketimine protects bovine heart submitochondrial particles (SMP) from the NADH-Fe(+3)-ADP-induced lipid peroxidation [8].

Chemical compound and disease context of Thiosine

• Growth of Serratia marcescens was not inhibited by high concentrations of L-lysine and its structural analogues, L-cancavanine and S-(2-aminoethyl)-L-cysteine (thialysine) [9].

Biological context of Thiosine

• Replacement of the active site base, Lys-258, with the weaker base, gamma-thia-Lys, does not alter the intrinsic pKa for the profiles of the Ki values for the maleate-E.PMP complexes or the kcat/K alpha-KGM values [10].
• Aminoethylcysteine ketimine decarboxylated dimer inhibits mitochondrial respiration by impairing electron transport at complex I level [11].
• The product of the spontaneous dimerization and decarboxylation of aminoethylcysteine ketimine (simply named the dimer in this note) has been investigated for a possible biochemical activity [11].
• Aminoethylcysteine ketimine decarboxylated dimer protects submitochondrial particles from lipid peroxidation at a concentration not inhibitory of electron transport [8].
• The enzymatic hydrolysis of this new substrate leads to the formation of S-cysteamine-3-pyruvate, which cyclizes in a non-rate-limiting step to give 2H-1,4-thiazin-5,6-dihydro-3-carboxylic acid (aminoethylcysteine ketimine), a compound exhibiting a strong absorption at 296 nm [12].

Anatomical context of Thiosine

• Effect of various aminoacid analogues on chick tendon procollagen synthesis and secretion: selective inhibition by S-2-aminoethyl cysteine [13].
• Determination of aminoethylcysteine ketimine decarboxylated dimer in human plasma and cultured cells by high-performance liquid chromatography with electrochemical detection [14].
• The ability of rabbit reticulocytes to degrade puromycin-peptides and aminoethylcysteine-induced aberrant polypeptides decreased during cellular maturation [15].
• Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide generation in human neutrophils [16].

Associations of Thiosine with other chemical compounds

• That aminoethylcysteine, but not other basic amino acids, can replace the function of lysine 267 documents both the importance of this residue and the requirement for a precisely positioned positive charge at the active site of the enzyme [17].
• High-performance liquid chromatography of cystathionine, lanthionine and aminoethylcysteine using o-phthaldialdehyde precolumn derivatization [18].
• The binding is removed by aminoethylcysteine ketimine and by cystathionine ketimine indicating the occurrence in bovine brain of a common binding site for ketimines [19].
• A promising candidate for the physiological substrate of SSAT2 is thialysine [S-(2-aminoethyl)-L-cysteine], which is acetylated predominantly at the epsilon-amino group with K(m) and kcat values of 290 muM and 5.2 s(-1) [20].
• However, lanthionine, 1,4-thiomorpholine-3,5-dicarboxylic acid, S-(2-aminoethyl)-L-cysteine and 1,4-thiomorpholine-3-carboxylic acid were without effect both on superoxide generation and on tyrosyl phosphorylation of 45 kDa protein [16].

Gene context of Thiosine

• Identification of aminoethylcysteine ketimine decarboxylated dimer, a natural antioxidant, in dietary vegetables [21].
• A 2.9-kb SacI fragment containing the ask-asd operon, encoding aspartokinase and aspartatesemialdehyde dehydrogenase, was cloned from an aminoethylcysteine-resistant, lysine-producing Corynebacterium lactofermentum strain [22].
• Antioxidant activity of aminoethylcysteine ketimine decarboxylated dimer on copper-induced LDL oxidation [23].

Analytical, diagnostic and therapeutic context of Thiosine

• The enzymatic method based on the inhibition of D-amino acid oxidase activity by aminoethylcysteine ketimine together with an high-performance liquid chromatography procedure confirm the identification and quantitations obtained with gas liquid chromatography [24].

References