Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.47 (cysteine synthase)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A technique based on resistance to azaserine was used to isolate mutants lacking O-acetylserine sulfhydrylase B, one of two enzymes in Salmonella typhimurium capable of synthesizing L-cysteine from O-acetyl-L-serine and sulfide. The mutant locus responsible for this defect has been designated cysM, and genetic mapping suggests that cysM is very close to and perhaps contiguous with cysA. Strains lacking either O-acetylserine sulfhydrylase B or the second sulfhydrylase, O-acetylserine sulfhydrylase A (coded for by cysK), are cysteine prototrophs, but cysK cysM double mutants were found to require cysteine for growth. O-Acetylserine sulfhydrylase B was depressed by growth on a poor sulfur source, and depression was dependent upon both a functional cysB regulatory gene product and the internal inducer of the cysteine biosynthetic pathway, O-acetyl-L-serine. Furthermore, a cysBc strain, in which other cysteine biosynthetic enzymes cannot be fully repressed by growth on L-cystine, was found to be constitutive for O-acetylserine sulfhydrylase B as well. Thus O-acetylserine sulfhydrylase B is regulated by the same factors that control the expression of O-acetylserine sulfhydrylase A and other activities of the cysteine regulon. It is not clear why S. typhimurium has two enzymes whose physiological function appears to be to catalyze the same step of L-cysteine biosynthesis.
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PMID:Regulation of O-acetylserine sulfhydrylase B by L-cysteine in Salmonella typhimurium. 38 18

A 1,2,4-triazole resistant mutant of S. typhimurium has been isolated, in which serine transacetylase activity is seven times higher than in wild type. Partially purified serine transacetylase from a strain carrying the trz-312 mutation has kinetic properties which are virtually identical to those of the wild type enzyme and binds to O-acetylserine sulfhydrylase A to form a cysteine synthetase complex which is also indistinguishable from that found in wild type. Thus the increased activity of serine transacetylase associated with trz-312 appears to result from increased quantities of a kinetically normal, enzyme protein. Resistance to 1,2,4-triazole is probably due to the ability of trz-312 strains to synthesize O-acetyl-L-serine at a rapid enough rate to compensate for that utilized by the O-acetylserine triazolylase reaction. Genetic mapping experiments, using P1-mediated transduction, show that trz-312 is 91-99% linked to cysE, the structural gene for serine transacetylase. The results of three point crosses indicate that this mutation is located at one extreme end of the cysE locus, as would be expected for a promotor mutation.
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PMID:A mutation affecting expression of the gene coding for serine transacetylase in Salmonella typhimurium. 79 Jan 54

Forteen species (17 strains) of phototrophic bacteria as well as one strain of Thiobacillus denitrificans were tested for cysteine synthase and S-sulfocysteine synthase. All strains contain cysteine sythase active with O-acetylserine; only the Chromatiaceae, two species of the Rhodospirillaceae and T. denitrificans contain S-sulfocysteine synthase. In six species repression by different sulfur compounds in the medium was studied. In Chromatium vinosum, cysteine synthase was found to be constitutive, while in the Rhodospirillaceae tested the enzyme is repressed by sulfide. Thiosulfate had a derepressive effect in Rhodopseudomonas globiformis but strongly repressed cysteine synthase in R. sulfidophila and R. palustris. Cysteine had only moderate effects with the species tested.
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PMID:Cysteine and S-sulfocysteine biosynthesis in phototrophic bacteria. 96 65

The inhibition of Salmonella typhimurium by 1,2,4-triazole appears to be mediated through an effect on L-cysteine biosynthesis. O-Acetylserine sulfhydrylase A, the final enzyme in the L-cysteine biosynthetic pathway, was found to catalyze a reaction (triazolylase) between O-acetyl-L-serine and 1,2,4-triazole, giving 1,2,4-triazole-1-alanine as a product. In wild type S. typhimurium grown on 4 mM 1,2,4-triazole, 97% of the total O-acetyl-L-serine synthesized in vivo is incorporated into 1,2,4-triazole-1-alanine. 1,2,4-triazole also significantly lowers the levels of several of the enzymes necessary for sulfate reduction. This effect is presumably due to the ability of the inhibitor to lower intracellular concentrations of O-acetyl-L-serine, an inducer of these enzymes. Inhibition of growth is probably caused by L-cysteine starvation, arising from the decreased availability of the L-cysteine precursors, sulfide and O-acetyl-L-serine. Two 1,2,4-triazole-resistant strains bearing mutations in cysK, the structural gene for O-acetylserine sulfhydrylase A, incorporate only small quantities of O-acetyl-L-serine into 1,2,4-triazole-1-alanine in vivo. In vitro studies, using purified preparations of O-acetylserine sulfhydrylase A, revealed greater losses of triazolylase activity than sulfhydrylase activity in the enzymes from both cysK mutants. Resistance to 1,2,4-triazole apparently can arise from mutations leading to a preferential loss of triazolylase activity or from mutations which diminish both activities to the extent that high concentrations of O-acetyl-L-serine and sulfide accumulate behind the sulfhydrylase reaction.
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PMID:Studies on the mechanism of inhibition of Salmonella typhimurium by 1,2,4-triazole. 110 Jun 24

O-Acetylserine (thiol) lyase, the last enzyme in the cysteine biosynthetic pathway, was purified to homogeneity from spinach leaf chloroplasts. The enzyme has a molecular mass of 68,000 and consists of two identical subunits of Mr 35,000. The absorption spectrum obtained at pH 7.5 exhibited a peak at 407 nm due to pyridoxal phosphate, and addition of O-acetylserine induced a considerable modification of the spectrum. The pyridoxal phosphate content was found to be 1.1 per subunit of 35,000, and the chromophore was displaced from the enzyme by O-acetylserine, leading to a progressive inactivation of the holoenzyme. Upon gel filtration chromatography on Superdex 200, part of the chloroplastic O-acetylserine (thiol) lyase eluted in association with serine acetyltransferase at a position corresponding to a molecular mass of 310,000 (such a complex called cysteine synthase has been characterized in bacteria). The activity of O-acetylserine (thiol) lyase was optimum between pH 7.5 and 8.5. The apparent Km for O-acetylserine was 1.3 mM and for sulfide was 0.25 mM. The calculated activation energy was 12.6 kcal/mol at 10 mM O-acetylserine. The overall amino-acid composition of spinach chloroplast O-acetylserine (thiol) lyase was different than that determined for the same enzyme (cytosolic?) obtained from a crude extract of spinach leaves. A polyclonal antibody prepared against the chloroplastic O-acetylserine (thiol) lyase exhibited a very low cross-reactivity with a preparation of mitochondrial matrix and cytosolic proteins suggesting that the chloroplastic isoform was distinct from the mitochondrial and cytosolic counterparts.
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PMID:Purification and characterization of O-acetylserine (thiol) lyase from spinach chloroplasts. 137 15

cDNA clones coding for hemoprotein H-450 were isolated from a rat liver cDNA library using anti-H-450 antibody. The molecular weight calculated from the deduced amino acid sequence comprising 547 amino acid residues was 60,085. The N-terminal sequence and a partial internal amino acid sequence of purified H-450, which were determined chemically, were both found in the amino acid sequence of H-450 deduced from the nucleotide sequence. H-450 mRNA is expressed in liver, kidney, and brain. A homology search of amino acid sequences indicated that H-450 shows no homology with cytochrome P-450, but shows significant homology with bacterial O-acetylserine (thiol)-lyases. However, H-450 has no O-acetylserine (thiol)-lyase activity.
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PMID:Molecular cloning and sequence analysis of cDNA coding for rat liver hemoprotein H-450. 208 36

The gene coding for O-acetylserine sulfhydrylase (OASS) from E. coli K12 was cloned into the vector pBR322 plasmid and expressed in a cysk mutant strain of E. coli that is deficient in O-acetylserine sulfhydrylase (OASS-). The clone containing the OASS gene was selected by using tetracycline-ammonium bismuth citrate medium. Retransformation of the hybrid plasmid into competent cysk mutant cells resulted in the recovery of a clone containing normal levels of O-acetylserine sulfhydrylase. Negative selection of retransformed cysk cells on 1,2,4-triazole plates resulted in the complete inhibition of growth indicating the presence of a functional OASS gene. The ability of the new clone to convert azide to its mutagenic metabolite was tested. Cultures of the clone cells containing significant levels of OASS activity were able to produce a mutagenic product from azide and O-acetylserine as tested on Salmonella typhimurium TA1530. This cloning method could be applied also to clone the same gene from eukaryotic sources.
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PMID:Cloning of the E. coli O-acetylserine sulfhydrylase gene: ability of the clone to produce a mutagenic product from azide and O-acetylserine. 212 44

Salmonella typhimurium strains (OASS-positive) synthesize a toxic but non-mutagenic metabolite from cyanide and O-acetylserine. Salmonella typhimurium mutant DW379 (OASS-deficient) is neither able to carry out this reaction in vitro nor produce the toxic metabolite in vivo. L-Cysteine reverses the cyanide metabolite mediated inhibition and thus allows OASS-positive strains to grow in medium containing cyanide and O-acetylserine. The results suggest that the enzyme O-acetylserine sulfhydrylase catalyzes the reaction of cyanide and O-acetylserine to form the toxic metabolite. This metabolite is ninhydrin-positive, adheres strongly to the cation-exchange column, and migrates in TLC to an Rf value similar to that of beta-cyanoalanine.
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PMID:Activation of sodium cyanide to a toxic but non-mutagenic metabolite in Salmonella typhimurium. 393 44

The ability of Arabidopsis, Drosophila and Neurospora to convert azide to its mutagenic metabolite was investigated. Cultures of these organisms all contained significant levels of O-acetylserine sulfhydrylase activity. Extracts from each organism produced a product from O-acetylserine and azide in vitro which was mutagenic in Salmonella typhimurium TA1530.
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PMID:In vitro production of azide mutagenic metabolite in Arabidopsis, Drosophila and Neurospora. 633 78

A mutagenic azide metabolite was purified from the medium in which Salmonella typhimurium cells were grown in the presence of azide. This metabolite was identified to be azidoalanine based on infrared and mass spectroscopy and elemental analysis. This compound appeared to be identical to the mutagenic compound synthesized in vitro from azide and O-acetylserine by partially purified O-acetylserine sulfhydrylase. The metabolite (azidoalanine) mutagenic efficiency and spectrum in S. typhimurium was similar to that of inorganic azide. The compounds 2-azidoethylamine, 2-bromoethylamine, 3-bromopropionic acid and N-(azidomethyl) phthalimide were also mutagenic with a similar spectrum to azide and azidoalanine, but with lower efficiency. The compounds 3-azidopropylamine, 4-azidobutylamine, 3-chloroalanine and ethylamine were only weakly or nonmutagenic. Numerous other chloro, bromo and azido phthalimide derivatives tested were nonmutagenic. It is suggested that the lack of azide mutagenicity (and perhaps carcinogenicity) in mammalian cells may be due to their inability to convert azide to azidoalanine.
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PMID:A mutagenic metabolite synthesized by Salmonella typhimurium grown in the presence of azide is azidoalanine. 635 13


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