Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ATP-sulfurylase, cysteine synthase, homocysteine synthase, arylsulfatase and beta-cystathionase in Saccharomycopsis lipolytica are repressed on the addition of methionine, homocysteine or cysteine to the growth medium. The use of appropriate mutants enabled us to demonstrate that the synthesis of these enzymes is regulated by the system involving at least two low-molecular weight effectors--most likely cysteine and methionine (or their close derivatives).
Mol Gen Genet 1979 Jul 02
PMID:Regulation of s-amino acids biosynthesis in Saccharomycopsis lipolytica. 28 1

Association of the apo-beta 2 and the holo-(beta-PLP)2 subunits of tryptophan synthase from Escherichia coli (L-serine hydro-lyase (adding indole) (EC 4.2.1.20)) with alpha subunits of the same enzyme has been studied by microcalorimetry. The results obtained from thermometric titrations clearly demonstrate that only the native complex alpha2beta 2 is formed, independent of an excess of alpha protein. The reaction of the holo-(beta-PLP)2 with alpha subunits at 25 degrees C is accompanied by a negative enthalpy change, which is almost twice as large as that for complex formation with the apo-beta 2 protein, thus indicating that the interaction enthalpy becomes more favorable in the presence of the coenzyme pyridoxal 5'-phosphate (PLP). Both reaction enthalpies show very large negative temperature coefficients, -3600 +/- 100 cal K-1 (Mol of beta 2)-1 being the value for the formation of the apoenzyme and -2300 +/- 100 cal K-1 (mol of beta 2)-1 pertaining to formation of the holoenzyme. The studies on the association of alpha and beta2 subunits in the two buffers revealed that at 25 degrees C approximately 0.75 proton are absorbed in the presence and absence of the coenzyme, whereas at 35 degrees C one proton is taken up from the solution when PLP is present, but two if the apo-beta 2 complex reacts. These results are a clear indication of energetic linkage between intersubunit interaction, hydrogen ion equilibria, and the binding of the coenzyme.
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PMID:Subunit interaction in tryptophan synthase of Escherichia coli: calorimetric studies on association of alpha and beta 2 subunits. 37 96

1. Methionine adenosyltransferase (ATP:L-methionine-S-adenosyl transferase, EC 2.5.1.6), cystathionine beta-synthase F1L-serine hydro-lyase (adding homocysteine), EC 4.2.1.22] and cystathionine gamma-lyase [L-cystathionine cysteine-lyase (deaminating), EC 4.4.1.1] activities were found only in the cytosol fraction of rat liver cells. None was found in the mitochondrial or endoplasmic reticulum fractions as judged by the distribution of marker enzymes on a density gradient after centrifugation of the cytoplasmic fraction of a liver homogenate, or in a preparation of liver cell nuclei. 2. Polymorphs, lymphocytes (with admixed monocytes) and mixed bone marrow white cells contained no methionine adenosyl transferase, cystathionine beta-synthase or cystathionine gamma-lyase activities. 3. The possible bearing of these results on the problem of abnormal cystine storage in cystinosis is briefly discussed.
Clin Sci Mol Med Suppl 1975 Jun
PMID:Methionine adenosyltransferase, cystathionine beta-synthase and cystathionine gamma-lyase activity of rat liver subcellular particles, human blood cells and mixed white cells from rat bone marrow. 105 81

Developmental changes in the activities of cystathionine beta-synthase and cystathionine gamma-lyase were measured in six regions of rat brain. On day-1, no differences were observed in the activities of cystathionine beta-synthase and cystathionine gamma-lyase among these regions, the values being about 40 nmol/h/mg protein, and 3 nmol/h/mg protein, respectively. Cystathionine beta-synthase activity increased gradually during development at almost the same rate in each region, reaching the adult level at week-4 (about 4-fold). Cystathionine gamma-lyase activity also increased during development, reaching adult level at week-2. But, the increase of enzyme activity in the cerebellum (about 1.8-fold) was clearly lower than that in the other regions (about 4-fold). Cystathionine gamma-lyase content in the various regions of week-3 rat brain estimated by immunoblotting was consistent with the enzyme activity, and the enzyme level in the cerebellum was lower than that in the other regions. Cystathionine content of cerebellum in week-3 increased rapidly during development, and was about five-fold more than that on day-1. However, cystathionine content in the other regions did not change during development. These findings indicated that at least one reason of the high content of cystathionine in the 3 weeks rat cerebellum was due to the low level of cystathionine gamma-lyase.
Biochem Mol Biol Int 1995 May
PMID:Changes in cystathionine gamma-lyase in various regions of rat brain during development. 749 71

Cystathionine beta-synthase (CBS) deficiency is an autosomal recessive disorder associated with multisystem clinical disease. We analyzed PCR amplified products from patients' RNA and genomic DNA. Direct sequencing of the entire coding region of the CBS gene revealed a G-919 to A transition in exon 8, resulting in replacement of Gly 307 by Ser (G307S) in the protein. The mutation was detected in one allele of patient L171 of French/Scottish ancestry and in both alleles of patient L198 of Irish ancestry. Amplifying and sequencing exon 8 from the genomic DNA showed that both parents of L198 were heterozygotes for G307S. The pathogenicity of the mutation was demonstrated in an expression experiment. The mutant protein was apparently stable in E.coli extracts and lacked catalytic activity. Sequencing of exon 8 revealed the G307S mutation in five additional families. All patients have pyridoxine nonresponsive homocystinuria. We have now observed this mutation in 9 of 52 apparently unrelated alleles of varied ethnic backgrounds. All 9 are from patients with Celtic (Irish/English/Scottish/French) ancestry in either one or both parents. The G307S mutation was detected in 50% (9 of 18) of the Celtic alleles in our series. The second mutation found in exon 8 is the I278T mutation, which was described previously in one allele of a pyridoxine responsive patient. This missense mutation was detected in one allele of a pyridoxine nonresponsive patient and in both alleles of a pyridoxine responsive patient. The latter suggests that I278T is probably associated with pyridoxine responsiveness.
Hum Mol Genet 1993 Nov
PMID:Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria. 750 2

Hyperhomocysteinemia occurs in approximately 30% of the patients with premature occlusive arterial disease (POAD). Some of these exhibit significantly reduced fibroblast cystathionine beta-synthase (CBS) activities, suggesting that they may be heterozygous for CBS deficiency. To test this possibility, we studied cDNA derived from four well characterized patients with POAD, exhibiting hyperhomocysteinemia and reduced CBS activities, from four normal controls, and from four obligatory heterozygotes for CBS deficiency. Lysates of individual colonies of E.coli, containing full-length PCR-amplification products in the expression vector, pKK388.1, were tested for CBS activity. cDNA from at least seven of the eight possible independent POAD alleles encoded catalytically active, stable CBS which exhibited normal response to both PLP and AdoMet. The sequences of all 3'-untranslated regions of all seven isolated POAD alleles were identical to the normal, 'wild-type' CBS sequences. The results of the expression studies were confirmed for one POAD patient by determining the full-length cDNA sequences for both alleles; these were entirely normal over the complete length of the cDNA. In contrast, the screening method correctly distinguished mutant from normal alleles in all four obligatory heterozygotes studied. We conclude that CBS mRNAs from POAD individuals are free from inactivating mutations, including all 33 previously identified in heterozygous carriers and homocystinuric patients.
Hum Mol Genet 1995 Apr
PMID:Hyperhomocysteinemia in premature arterial disease: examination of cystathionine beta-synthase alleles at the molecular level. 763 11

Cystathionine beta-synthase (CBS) deficiency is the major cause of homocystinuria in humans. The most frequent symptoms of homocystinuria include: dislocated optic lenses, vascular disorders, skeletal abnormalities and mental retardation. Patients with this deficiency have elevated levels of homocyst(e)ine, methionine and low cysteine in their body fluids. These abnormal levels often partially or fully normalize upon treatment with pharmacological doses of vitamin B6. To investigate the molecular and biochemical basis for these conditions, it was necessary to determine the nucleotide and polypeptide sequence of CBS. We report here the human CBS cDNA sequence of 2,554 nucleotides encoding the CBS subunit of 551 amino acids. An intron of 214 bp appears to be retained in the 3'-untranslated region of most of the fibroblast and liver mRNA. We also report a frequent Mspl polymorphism in the 3'-untranslated sequence and two synonymous mutations in the coding region: 699C/T (Y233Y) and 1080C/T (A360A). The amino acid sequence similarity of human and rat CBS is greater than 90%; the enzyme also exhibits 52% similarity to O-acetylserine(thiol)-lyase from bacteria and plants. Lastly, we demonstrate that expression of the human enzyme in CHO cells yields enzymatically active protein of the expected size with a half-life of approximately 14 hrs.
Hum Mol Genet 1993 Oct
PMID:Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells. 790 80

We determined the molecular basis of cystathionine beta-synthase (CBS) deficiency in three siblings with pyridoxine responsive homocystinuria using a significantly improved mutation screening method in bacteria. The phenotypic expression of the siblings differed even though their CBS genotypes were identical. The paternal allele contained a linked pair of mutations, C233G and G306C, corresponding to P78R and K102N in the polypeptide chain. Together, these inactivated the enzyme; however, expressed separately, they reduced activity by about one half. The single maternal mutation G715A (E239K) effectively abolished CBS activity. Subunits of CBS were absent from patient fibroblast extracts; however, E. coli, transformed with plasmids containing patient CBS cDNA, expressed the subunits, although in reduced amounts. The mother, an obligate heterozygote, was free from all signs of homocystinuria; nonetheless, extracts of her fibroblasts were devoid of CBS protein and activity. We conclude that fibroblast levels of CBS are only partially effective as prognosticators of disease severity and that it is important to test the in vivo response to vitamin B6 in all cases of homocystinuria, including those in which the mutations lead to the absence of the enzyme in cultured fibroblasts.
Hum Mol Genet 1994 Jul
PMID:Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system. 798 78

We have isolated cDNA clones encoding cysteine synthase (CSase, EC 4.2.99.8), which catalyzes the terminal step in cysteine biosynthesis, by direct genetic complementation of a Cys- mutation in Escherichia coli with an expression library of Citrullus vulgaris (watermelon) cDNA. The library was constructed from 8-day-old etiolated seedlings of C. vulgaris in the lambda ZAPII vector, converted to a plasmid library by in vivo excision, and then used for transformation of cysteine auxotroph E. coli NK3, which lacks the cysK and cysM loci. The complementing cDNA containing a 560 bp 5'-untranslated region encodes a polypeptide of 325 amino acids of M(r) 34342. The translational product reacted with an antibody raised against CSase A of Spinacia oleracea. CSase and beta-pyrazolealanine synthase activities were demonstrated in vitro in extracts from E. coli cells expressing the cDNA. Genomic DNA blot analysis indicated the presence of a single copy of the gene, designated cysA, in the C. vulgaris genome. RNA blot hybridization indicated constitutive expression of cysA in cotyledons, hypocotyls and radicles of green and etiolated seedlings. These data suggested that this cDNA clone encodes CSase A the homolog of which in spinach is localized in the cytoplasm. The molecular phylogenetic tree of the amino acid sequences of CSases from plants and bacteria suggested that there are three families in the CSase superfamily; the plant CSase A family, the plant CSase B family and the bacterial CSase family. The proteins in the plant CSase A family are the most conserved relative to the ancestral CSase protein.
Mol Gen Genet 1994 Jul 08
PMID:Molecular cloning of a cysteine synthase cDNA from Citrullus vulgaris (watermelon) by genetic complementation in an Escherichia coli Cys- auxotroph. 804 62

Mutations in the human cystathionine beta-synthase (CBS) gene are known to cause homocystinuria and may also be a significant risk factor for premature atherosclerosis. We have previously shown that the human CBS protein can substitute for the endogenous yeast CBS protein in Saccharomyces cerevisiae. We now show that expression of three different CBS mutants known to be associated with reduced enzyme activity in humans fail to complement growth in the yeast assay. In addition, we have used the yeast CBS assay to identify eight mutant CBS alleles in cell lines from patients with CBS deficiency. These mutant alleles include two previously identified and five novel CBS mutations. Our results also demonstrate that the yeast CBS assay can detect a large percentage of individuals heterozygous for mutations in CBS. This system should be useful in determining the relationship between CBS mutations and human disease.
Hum Mol Genet 1995 Jul
PMID:A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene. 852 2


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