1.1.1.3 (2S)-2-[[4-(propan-2-yl)phenyl]sulfanyl]propanenitrile - 215936 1.1.1.3 1-tert-butyl-4-[(difluoromethyl)sulfanyl]benzene - 216163 1.1.1.3 1-[(1S,2S)-2-(bromomethyl)cyclopropyl]-4-[(trifluoromethyl)sulfanyl]benzene - 216142 1.1.1.3 2,2'-[thiobis[[2-(1,1-dimethylethyl)-5-methyl-4,1-phenylene]oxy]]bis-acetic acid diethyl ester - 119037 1.1.1.3 3-[(4-tert-butylphenyl)sulfanyl]propane-1-thiol - 216343 1.1.1.3 4,4'-sulfanediylbis[2-(propan-2-yl)phenol] - 217313 1.1.1.3 4,4'-thiobis[2-(1,1-dimethylethyl)]-5-methyl-phenol - 119034 1.1.1.3 4,4'-thiobis[2-(1,1-dimethylethyl)]-phenol - 119032 1.1.1.3 4,4'-thiobis[2-(1-methylethyl)]-phenol - 122915 1.1.1.3 4,4'-thiobis[5-methyl-2-(1-methylethyl)]-phenol - 119033 1.1.1.3 4,4'-[1,2-ethanediylbis(thio)]bis[2,6-bis(1-methylpropyl)]-phenol - 122918 1.1.1.3 4,4'-[1,2-ethanediylbis(thio)]bis[2-(1,1-dimethylethyl)-6-methyl]-phenol - 122917 1.1.1.3 4-(1-methylheptyl)-1,3-benzenediol - 119041 1.1.1.3 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol - 217312 1.1.1.3 4-[[2-(2-furanyl)ethyl]thio]-phenol - 119040 1.1.1.3 4-[[[4-(1,1-dimethylethyl)phenyl]thio]methyl]-2,6-bis(1-methylethyl)-phenol - 119035 1.1.1.3 aspartate - 724 1.1.1.3 bis(4-chlorophenyl)ethyloxiranyl-silane - 122916 1.1.1.3 DL-allo-threonine - 93266 1.1.1.3 EGTA - 173 1.1.1.3 H-(1,2,4-triazol-3-yl)-DL-alanine - 106245 1.1.1.3 homoserine - 5553 1.1.1.3 L-cysteine - 74 1.1.1.3 L-serine - 95 1.1.1.3 L-threonine - 250 1.1.1.3 lysine - 1107 1.1.1.3 methionine - 692 1.1.1.3 NADP+ - 10 1.1.1.3 p-chloromercuribenzoate - 43 1.1.1.3 Thr - 3496 1.1.1.3 Trifluoperazine - 977 1.1.1.3 Tris - 317 1.1.1.3 [2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid ethyl ester - 119036 1.1.1.3 L-serine 14% inhibition at 10 mM 95 1.1.1.3 Thr 90% inhibition of homoserine dehydrogenase 2 at 10 mM 3496 1.1.1.3 NADH acts as a competitive inhibitor of NAD+, product inhibition, non-competitive inhibition versus L-homoserine 8 1.1.1.3 L-serine allosteric inhibitor 95 1.1.1.3 L-threonine allosteric inhibitor 250 1.1.1.3 L-lysine allosteric regulation of recombinant engineered homoserine dehydrogenase by nonnatural inhibitor L-lysine 134 1.1.1.3 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol competitive to L-aspartate 4-semialdehyde, enzyme binding structure anaysis from crystal structure, overview 217312 1.1.1.3 L-cysteine competitive versus L-homoserine, uncompetitive versus cofactors NAD+ and NADP+. 95% inhibition at 10 mM. The feedback inhibition of StHSD by cysteine occurs through the formation of an enzyme-NAD-cysteine complex. Cysteine situates within the homoserine binding site, formation of a covalent bond between cysteine and the nicotinamide ring. Cysteine interacts with six residues (Gly156, Thr157, Tyr183, Glu185, Asp191, and Lys200) in the StHSD active site, binding structure analysis, overview 74 1.1.1.3 L-threonine degree of inhibition depends on age of plant; sensitive and insensitive isozymes 250 1.1.1.3 additional information enzyme is not inhibited by other aspartate-derived amino acids than threonine 2 1.1.1.3 threonine feedback inhibition, one isozyme is resistant and another is sensitive to threonine inhibition, 46.9% inhibition at 1 mM, 63.9% at 5 mM 2764 1.1.1.3 5-hydroxy-4-oxo-L-norvaline HONV, the mechanism of antifungal action of HONV dipeptides (determined against Candida albicans strain ATCC 10231 cells in three different growth media) involves uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. Chemical synthesis of HONV and construction of HONV dipeptides as potential antifungal agents, overview. Six dipeptides with L-alanine, L-valine, L-norvaline (Nva), L-leucine, L-isoleucine, and L-phenylalanine as the N-terminal residues are obtained, Gly-HONV and D-Leu-HONV are synthesized and evaluated for comparative purposes. Antifungal in vitro activity and MIC values of HONV and its dipeptides, overview. Activity of HONV strongly depends on growth medium composition. Dipeptide (S)-2-N-[(R)-leucyl]amino-5-hydroxy-4-oxopentanoic acid (D-Leu-HONV) is inactive in all growth media. Antifungal activity of the compounds against different Candida species. Lack of activity of HONV-containing dipeptides against the Candida albicans opt1-opt5DELTA ptr2DELTA ptr22DELTA mutant clearly indicates that these compounds are transported to Candida albicans cells by the oligopeptide transport system, most probably by the di-tripeptide permeases Ptr2p and Ptr22, uptake rates into Candida albicans strain ATCC 10231 cells at pH 5.0 and pH 7.0 are determined, the initial uptake velocities are generally higher at pH 5.0 than at pH 7.0 46992 1.1.1.3 glycyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-glycylamino-5-hydroxy-4-oxopentanoic acid 255925 1.1.1.3 L-alanyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-[(S)-alanyl]amino-5-hydroxy-4-oxopentanoic acid 255939 1.1.1.3 L-isoleucyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-[(S)-isoleucyl]amino-5-hydroxy-4-oxopentanoic acid 255940 1.1.1.3 L-leucyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-[(S)-leucyl]amino-5-hydroxy-4-oxopentanoic acid 255941 1.1.1.3 L-norvalyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-[(S)-norvalyl]amino-5-hydroxy-4-oxopentanoic acid 255942 1.1.1.3 L-phenylalanyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-[(S)-phenylalanyl]amino-5-hydroxy-4-oxopentanoic acid 255943 1.1.1.3 L-valyl-5-hydroxy-4-oxo-L-norvaline i.e. (S)-2-N-[(S)-valyl]amino-5-hydroxy-4-oxopentanoic acid 255944 1.1.1.3 additional information inhibitor docking study, overview 2 1.1.1.3 additional information L-homoserine inhibits the activity of aspartokinase encoded by metL 2 1.1.1.3 additional information L-homoserine oxidation of the Thermotoga maritima enzyme is almost impervious to inhibition by L-threonine, while L-threonine inhibits AK activity in a cooperative manner. The distinctive sequence of the regulatory domain in Thermotoga maritima AK-HseDH is likely responsible for the unique sensitivity to L-threonine. The quaternary structure of this enzyme is not affected by L-threonine 2 1.1.1.3 additional information Lys, Met, and S-2-aminoethyl-L-cysteine do not affect HSDH activity at 1-5 mM 2 1.1.1.3 itraconazole MIC value against strain Pb18 is 0.007 mg/ml 2302 1.1.1.3 Amphotericin B MIC value against strain Pb18 is 0.06 mg/ml 5518 1.1.1.3 Amphotericin B MIC value against strain Pb18 is 0.12 mg/ml 5518 1.1.1.3 Zinc203432 MIC value is 0.032 mg/ml 256303 1.1.1.3 Zinc203432 MIC value is 0.064 mg/ml 256303 1.1.1.3 Zinc273730 MIC value is 0.064 mg/ml 256310 1.1.1.3 Zinc273730 MIC value is 0.064. Zinc273730 makes important contacts with Gly215, Tyr216, Thr217, and Glu218 256310 1.1.1.3 Zinc2123137 MIC/MCF is 0.008 mg/ml 256307 1.1.1.3 Zinc15967722 MIC/MCF is 0.032 mg/ml 256301 1.1.1.3 Zinc20611644 MIC/MCF is 0.128 mg/ml 256304 1.1.1.3 additional information molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Synergistic effects of HS1 and HS2 in combination with itraconazole against Paracoccidioides brasiliensis. Zinc1531037 and Zinc52986906 are not inhibitory 2 1.1.1.3 additional information molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 Molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Zinc1531037 and Zinc52986906 are not inhibitory 2 1.1.1.3 NADP+ NADP+ does not act as a cofactor for this enzyme, but as a strong inhibitor of NAD+-dependent oxidation of Hse, evaluation of the factors responsible for the NADP+-mediated inhibition 10 1.1.1.3 additional information no inhibition by [2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid and 4-amino-butyric acid 2-tert-butyl-4-(3-tert-butyl-4-hydroxy-phenylsulfanyl)-phenyl ester 2 1.1.1.3 L-threonine not inhibitory 250 1.1.1.3 additional information PbHSD inhibitor screening using the Zinc library, molecular dynamics simulations of PbHSD and ligand docking, electrostatic contacts between protein residues and the respective ligand atoms, overview. The selected ligands remain bound to the protein by a common mechanism throughout the simulation. Cytotoxicity evaluation in HeLa and Vero cells 2 1.1.1.3 (S)-2-amino-4-oxo-5-hydroxypentanoic acid RI-331 48379 1.1.1.3 L-threonine sensitive and insensitive isozymes 250 1.1.1.3 D-threonine slight 1718 1.1.1.3 L-cysteine slight 74 1.1.1.3 L-cysteine slight inhibition of chloroplast isozyme, strong inhibition of cytoplasmic isozyme 74 1.1.1.3 L-threonine strong inhibition of both enzyme activities, aspartate dehydrogenase and aspartate kinase activity, by decreasing the affinity of the enzyme for substrate and cofactors, kinetic effects 250 1.1.1.3 L-threonine the enzyme activity is subjected to feedback regulation by L-threonine 250 1.1.1.3 threonine the methionine-producing strain contains a deregulated homoserine dehydrogenase that is not sensitive to feedback inhibition as the wild-type enzyme 2764 1.1.1.3 additional information the natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine 2 1.1.1.3 L-threonine the natural threonine binding sites of the enzyme are predicted and verified by mutagenesis experiments 250 1.1.1.3 L-threonine the regulatory domain of the enzyme contains 2 binding sites, interaction with Gln443 leads to inhibition of the aspartate kinase activity and facilitates the binding of a second threonine on Gln524 leading to inhibition of the homoserine dehydrogenase activity, inhibition of the forward reactions 250 1.1.1.3 additional information Thr does not inhibit homoserine dehydrogenase 1 2 1.1.1.3 additional information tHSD is poorly inhibited by less than 5% by 10 mM L-methionine, L-isoleucine, or L-threonine, all of which are final products in the aspartate pathway, and by L-lysine 2 1.1.1.3 L-threonine weakly inhibits reverse but not forward reaction 250 1.1.1.3 methionine weakly inhibits reverse but not forward reaction 692