Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked ichthyosis (XLI) is an inborn error of metabolism caused by steroid sulfatase (STS) deficiency. In more than 80% of XLI patients the enzyme deficiency is due to large deletions involving the entire STS gene and flanking sequences. However, some patients with the classical XLI phenotype and complete STS deficiency do not show any detectable deletions by Southern blot analysis using full-length STS cDNA as a probe. We have studied five unrelated patients who are such "nondeletion" mutants. Western blot analysis using anti-STS antibodies was performed on patients' fibroblast extracts and revealed absence of cross-reacting material. First-strand cDNA synthesis by reverse transcription from patients' RNA isolated from cultured fibroblasts and PCR amplification of overlapping segments of the entire STS polypeptide coding region were performed. Three point mutations were identified by chemical mismatch cleavage, sequenced by dideoxynucleotide chain-termination sequencing and confirmed by allele-specific oligonucleotide hybridization of the patients' genomic DNA. The mutations resulted in the substitution of a tryptophan for an arginine at codon 1319, changing a hydrophobic to a basic hydrophilic amino acid, the substitution of a cysteine for a tyrosine at codon 1542, potentially losing a disulfide bond, and the substitution of a serine for a leucine at codon 1237. These are the first point mutations to be documented in the STS gene and may allow insight into functionally important domains of the protein.
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PMID:Identification of point mutations in the steroid sulfatase gene of three patients with X-linked ichthyosis. 153 90

A yellow-colored protein (YCP) was isolated from the hemolymph (i.e. blood) of fifth instar wandering stage larvae of Manduca sexta. The molecular mass of YCP was 31 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gel filtration chromatography suggested that native YCP was a monomer. The absorbance spectrum of YCP revealed maxima at 278 and 405 nm. Chromophore was released from YCP through denaturation of the protein with methanol and chloroform. In neutral solution and in acid, the released chromophore showed the absorbance characteristics of an ommochrome: ommatin D. In addition, the chromophore was sensitive to treatment with arylsulfatase as would be expected for ommatin D. The amino acid composition and the N-terminal sequence of YCP were determined. The YCP polypeptide chain was found to be glycosylated. Carbohydrate analysis suggested that Man and GlcNAc were present in a 3:1 ratio. Circular dichroism indicated that YCP consisted of 68% beta-pleated sheet with no alpha-helices being detected. An in vitro incubation of larval fat body in the presence of [35S]methionine indicated that this organ was the site of synthesis. Ommochromes arise in insects as end products of the metabolism of tryptophan. It is well-documented that ommochromes occur in both the tissues and the excreta of insects. We propose that in M. sexta, one such tryptophan metabolite is found in the hemolymph associated with a specific protein.
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PMID:Purification and properties of an ommochrome-binding protein from the hemolymph of the tobacco hornworm, Manduca sexta. 193 73

Rabbit liver arylsulfatase A (aryl-sulfate sulfhydrolase, EC 3.1.6.1) monomers of 130 kDa contain two free sulfhydryl groups as determined by spectrophotometric titration using 5,5'-dithiobis(2-nitrobenzoate) and by labeling with the fluorescent probe 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid. Fluorescence quenching data indicate that the reactive sulfhydryl is present in proximity to one or more tryptophan residues. Chemical modification of the sulfhydryl groups does not alter the distinctive pH-dependent aggregation property of the arylsulfatase A. The free sulfhydryls of the enzyme react with numerous sulfhydryl reagents. Based on the reactions of iodoacetic acid, methyl methanethiosulfonate, 5,5'-dithiobis(2-nitrobenzoate) and 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid with the sulfhydryl groups of arylsulfatase A, it is concluded that free sulfhydryls are not essential for the enzyme activity. In contrast, the observed inactivation of the enzyme by p-hydroxymercuribenzoate or p-hydroxymercuriphenylsulfonate is probably due to a modification of a histidine residue, consistent with previous reports that histidine is near the active site of arylsulfatase A. p-Hydroxymercuribenzoate and p-hydroxymercuriphenylsulfonate are able to react both with cysteine and with histidine residues of the protein molecule.
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PMID:Sulfhydryl groups of rabbit liver arylsulfatase A. 286 83

The enzyme activities of four strains of Legionella pneumophilia were investigated by using the API ZYM system (API System S.A., F-38390 Montalieu Vercieu, France) and synthetic substrates. Aminopeptidases were detected specifically against L-alanine, L-arginine, L-aspartic acid, L-cystine, L-glutaminic acid, glycine, L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-tryptophan, L-tyrosine, and L-valine. Furthermore, the bacteria possesses esterase activity splitting propionate, butyrate, caproate, caprylate, and caprate, but not laurate, myristate, palmitate, and stearate, esters. The enzymes studies were inhibited partially by aprotinin. No inhibition of phosphatase (pH range, 5.4 to 8.5) or of phosphoamidase was observed. Activities of arylsulfatase, chymotrypsin, trypsin, and glycosidases could not be detected.
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PMID:Enzymatic profile of Legionella pneumophilia. 616 35

A number of arylamines (including tyramine and tryptamine) increased the in vitro activity of arylsulfatase from Pseudomonas sp. strain C12B. Amino acid analogs of these amines (e.g., tyrosine and tryptophan) failed to exert an effect. Stimulation of activity by tyramine could not be accounted for in terms of sulfotransferase activity for this phenol, and no shift in the pH optimum for the enzyme occurred in the presence of tryptamine. Increased Vmax due to these amines was independent of enzyme concentration but varied significantly with substrate concentration. Evidence is presented which suggests that arylamines enhance arylsulfatase activity by forming a salt linkage with the substrate and rendering it more susceptible to enzymatic and acid-catalyzed hydrolyses. The recrystallized tryptamine salt of the substrate exhibited a reduced affinity for the enzyme but was hydrolyzed more rapidly than the potassium salt, which is normally employed as the assay substrate.
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PMID:Stimulation of bacterial arylsulfatase activity by arylamines: evidence for substrate activation. 724 96

A new, 'diffuse, multiple banding', electrophoretic variant of arylsulfatase A protein was found in two patients with major depression. Protein analyses showed that this variant and the normal enzyme differed in amino acid sequence and/or post-translational modifications unrelated to phosphate groups and oligomannose glycans. Analysis of the arylsulfatase A genes from a subject with the new variant identified three mutations; one gene had the two mutations associated with arylsulfatase A pseudodeficiency, and the other had a G to T transversion which changes a tryptophan to cysteine in the protein. These mutations result in an arylsulfatase A protein heteromer with diffuse electrophoretic banding. The possible association of these mutations with major depression is discussed.
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PMID:A novel arylsulfatase A protein variant and genotype in two patients with major depression. 889 13

The plastic of urinary catheter drainage bags occasionally turns purple hours or days after catheterization and the color becomes increasingly intense the longer the same drainage system is left in place. This phenomenon was first reported in 1978 as "purple urine bag syndrome", and had been known to occur with bacterial infection of the urinary tract with chronic constipation. Chronic constipation is commonly associated with bacterial overgrowth in the bowel in which tryptophan has been converted to indol and yields the high levels of indigo (blue) and indirubin (red) in urinary bags of patients with bacterial infection of the urine, because indigo-producing bacteria have indoxyl phosphatase or sulfatase that can produce indigo and indirubin. We determined the serum levels of amino acids in patients with purple urine bag syndrome. The serum level of tryptophan and valine were significantly reduced in patients with purple urine bag syndrome. This result suggests that absorption of amino acids was affected by disturbances of colonic motility and intestinal bacterial overgrowth.
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PMID:[Serum levels of amino acid in patients with purple urine bag syndrome]. 928 12

Here the structure of human glyoxalase II has been investigated by studying unfolding at equilibrium and refolding. Human glyoxalase II contains two tryptophan residues situated at the N-terminal (Trp57) and C-terminal (Trp199) regions of the molecule. Trp57 is a non-conserved residue located within a "zinc binding motif" (T/SHXHX57DH) which is strictly conserved in all known glyoxalase II sequences as well as in metal-dependent beta-lactamase and arylsulfatase. Site-directed mutagenesis has been used to construct single-tryptophan mutants in order to characterize better the guanidine-induced unfolding intermediates. The denaturation at equilibrium of wild-type glyoxalase II, as followed by activity, intrinsic fluorescence and CD, is multiphasic, suggesting that different regions of varying structural stability characterize the native structure of glyoxalase II. At intermediate denaturant concentration (1.2 M guanidine) a molten globule state is attained. The reactivation of the denatured wild-type enzyme occurs only in the presence of Zn(II) ions. The results show that Zn(II) is essential for the maintenance of the native structure of glyoxalase II and that its binding to the apoenzyme occurs during an essential step of refolding. The comparison of unfolding fluorescence transitions of single-trypthophan mutants with that of wild-type enzyme indicates that the strictly conserved "zinc binding motif" is located in a flexible region of the active site in which Zn(II) participates in catalysis.
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PMID:Unfolding and refolding of human glyoxalase II and its single-tryptophan mutants. 1043 33

2-amino-9H-pyrido[2,3-b]indole (AalphaC) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems AalphaC can be formed by pyrolysing either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of AalphaC in rats was investigated. Rats were dosed with tritium labelled AalphaC. Urine and faeces were collected over three days. The metabolites of AalphaC were characterised by HPLC-MS and quantified by liquid scintillation counting. Conjugated metabolites were characterised by enzymatic hydrolyses with beta-Glucuronidase or arylsulfatase. The data showed that the metabolic pattern of AalphaC was similar in all rats. About 55% of the dose was excreted in urine and faeces during 72 h and the major amount of AalphaC metabolites (31%) was excreted during the first 24 h. In addition to a small amount of unmetabolised AalphaC seven conjugated metabolites were characterised. Three minor metabolites were characterised as AalphaC-N(2)-glucuronide and glucuronic acid conjugates of 3-OH-AalphaC and 6-OH-AalphaC. Four metabolites were all characterised as sulphuric acid conjugates and accounted for the largest amount of metabolites excreted in urine. The two major sulphuric acid conjugates were identified as AalphaC-3-O-sulfate and AalphaC-6-O-sulfate, while the minor sulphuric acid conjugates were proposed to be other O-sulfonated metabolites. In faeces only AalphaC was excreted and accounted for about 12% of dose during the first 24 hours. Any activated metabolites of AalphaC were not detected in rat urine or faeces. In future accumulation or binding of AalphaC to macromolecules such as DNA and proteins has to be studied.
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PMID:Excretion of metabolites in urine and faeces from rats dosed with the heterocyclic amine, 2-amino-9H-pyrido[2,3-b]indole (AalphaC). 1511 96

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeA alpha C in rats was investigated. Rats were dosed with tritium-labeled MeA alpha C, and urine and feces were collected over 3 days. The metabolites of MeA alpha C were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with beta-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeA alpha C was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeA alpha C-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeA alpha C and two phase I metabolites, 6-OH-MeA alpha C and 7-OH-MeA alpha C, the following conjugated metabolites were identified: MeA alpha C-N(2)-glucuronide, A alpha C-3-CH(2)O-glucuronide, 3-carboxy-A alpha C and 3-carboxy-A alpha C-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeA alpha C and 7-OH-MeA alpha C. Also, a large amount of a rather unstable compound proposed to be of MeA alpha C-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeA alpha C and 7-OH-MeA alpha C were the only compounds identified in feces. Any activated metabolites of MeA alpha C were not detected in rat urine or feces.
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PMID:Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C). 1515 58


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