Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat liver N-hydroxy-2-acetylaminofluorene (N-OH-2AAF) sulfotransferase activity is mediated by aryl sulfotransferase IV (AST IV) and causes the bioactivation of N-OH-2AAF to a highly reactive sulfuric acid ester form putatively capable of inducing liver cancer. Dietary administration of 2-acetylaminofluorene (2AAF) to induce hepatocarcinogenesis in rats has been shown to cause a rapid loss in N-OH-2AAF sulfotransferase activity. A possible mechanism for the in vivo loss in sulfotransferase activity may be the PAPS-dependent, sulfotransferase-catalyzed, reaction product inactivation of the enzyme by covalent reaction with the N-OH-2AAF sulfuric acid ester. In vitro studies to evaluate this possibility utilized a highly purified form of AST IV and measured the extent of PAPS-dependent interaction between the enzyme and N-OH-2[9-14C]AAF. The results showed the presence of a adenosine-3'-phospho-5'-phosphosulfate (PAPS)-dependent 14C-labeling of AST IV. The labeling could be blocked if the sulfotransferase inhibitor pentachlorophenol was present. Analysis of 14C-labeled AST IV following alkaline digestion and chromatography of digestion products indicated that AST IV cysteine and methionine residues were primary sites of 2[9-14C]AAF adduction. Studies involving the pretreatment of AST IV with PAPS and N-OH-2AAF prior to the measurement of N-OH-2AAF sulfotransferase activity showed a close parallel between formation of the AST IV cysteine-2AAF adduct and loss of activity. Similar studies showed that enzyme inactivation and cysteine-2AAF adduct formation could be blocked when excessive amounts of a competing nucleophile, methionine, were present during the pretreatment step, suggesting that inactivation does not proceed by a mechanism-based process. Finally, experiments involving prior reaction of AST IV with the thiol-blocking agent, N-ethylmaleimide, before measurement of enzyme activity showed essentially full loss of sulfotransferase activity and suggested that formation of AST IV cysteine-2AAF adducts could be a mechanism for enzyme inactivation. These results indicate that the in vitro inactivation of AST IV by the reactive N-OH-2AAF sulfuric acid ester is accompanied by covalent binding to AST IV, possibly through the formation of cysteine-2AAF adducts, and suggests that this mechanism merits further consideration as a basis for the loss of N-OH-2AAF sulfotransferase activity in vivo.
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PMID:Reaction product inactivation of aryl sulfotransferase IV following electrophilic substitution by the sulfuric acid ester of N-hydroxy-2-acetylaminofluorene. 173 62

Phenol sulfotransferases catalyze the transfer of a sulfonate moiety from 3'-phosphoadenosyl 5'-phosphosulfate to a phenolic group of lipophylic substrates to generate soluble sulfate esters. Using a phenol sulfotransferase cDNA as probe to screen a human leukocyte genomic DNA library constructed in lambda EMBL3, we obtained a clone containing a complete gene sequence. Comparison of the gene sequence with that of the corresponding cDNAs, namely phenol-sulfating phenol sulfotransferase (P-PST) or thermostable sulfotransferase (TS-PST), and human aryl sulfotransferase 1 and 2 (HAST1 and HAST2) indicates that the gene possesses eight short exons separated by seven introns included in approximately 5 kb. HAST2 has a different 5' untranslated sequence, and thus is encoded by a different mRNA species. While the nucleotide sequence corresponding to the 5' noncoding region of P-PST (TS-PST and HAST1) is included in the exon I, the 5' untranslated sequence of HAST2 is located in the beginning of exon IIa. The remaining sequence in exon II that is identical to both P-PST and HAST2 was termed exon IIb. Exons III to VIII, which cover the coding region and the 3' untranslated region, are almost identical in all types of PST or AST cDNAs. These results suggest that the phenol sulfotransferase gene possesses two alternate promoters that drive the expression of the two different mRNA species in a tissue-specific manner. Transfection of chloramphenicol acetyl transferase (CAT) reporter gene vectors containing the 5'-flanking sequence upstream from exon I and exon II, respectively, in transformed human embryonal kidney (293) cells indicate that both sequences possess promoter activity with higher activity for promoter 1. RNA blot analysis indicates that human phenol sulfotransferase gene is expressed in kidney, liver, lung, leukocyte, colon, small intestine, and spleen.
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PMID:Human phenol sulfotransferase gene contains two alternative promoters: Structure and expression of the gene. 892 11

Cytosolic sulfotransferases (SULT) catalyze the sulfation of structurally diverse drugs, endogenous compounds and xenobiotics. These reactions involve the transfer of a sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the hydroxyl/amino groups of acceptor molecules. Although sulfate conjugation is generally considered as a detoxication pathway producing more water-soluble and often less toxic metabolites, sulfation of certain classes of compounds produce sufficiently electrophilic metabolites that can covalently bind to cellular macromolecules, DNA and RNA. The important roles of electrophilic sulfate ester metabolites in the metabolic activation, mutagenicity and ultimate carcinogenicity of many xenobiotics have been considerably elucidated. Examples include the class of hydroxymethyl polycyclic aromatic hydrocarbons, allylic alcohols, N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines. Results obtained by many scientists during the last two decade correlate with a hypothesis that electrophilic sulfate esters may be the major ultimate carcinogenic forms of many, if not most, procarcinogens derived from benzylic/allylic alcohols and hydroxy arylamines. Careful analysis of these results suggest that the activities of human hydroxysteroid sulfotransferase (hHST), and a related form in rat liver, rat hydroxysteroid sulfotransferase a (STa), as well as aryl sulfotransferases both from rat and human liver, account for a substantial portion of the activation of benzylic/allylic alcohols in these species. Moreover, aryl sulfotransferases have also been indicated as the responsible SULT family in the bioactivation of hydroxy arylamines in the liver of different species including human. Molecular cloning of the individual sulfotransferases and expression of these individual forms in heterologous expression systems have allowed us to better understand the role of SULTs in the bioactivation of different procarcinogens and the form of sulfotransferase involved in their bioactivation. Additional structure-activity studies with homogeneous forms of rat liver STa and AST IV have also yielded comparative insight into some of the parameters important in recognition of substrates and inhibitors by these enzymes.
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PMID:Current status of the cytosolic sulfotransferases in the metabolic activation of promutagens and procarcinogens. 1146 78

Arylsulfotransferase (AST, EC 2.8.2.22), an enzyme capable of sulfating a wide range of phenol-containing compounds was purified from a Clostridium innocuum isolate (strain 554). The enzyme has a molecular weight of 320 kDa and is composed of four subunits. Unlike many mammalian and plant arylsulfotransferases, AST from Clostridium utilizes arylsulfates, including p-nitrophenyl sulfate, as sulfate donors, and is not reactive with 3-phosphoadenosine-5'-phosphosulfate (PAPS). The enzyme possesses broad substrate specificity and is active with a variety of phenols, quinones and flavonoids, but does not utilize primary and secondary alcohols and sugars as substrates. Arylsulfotransferase tolerates the presence of 10 vol% of polar cosolvents (dimethyl formamide, acetonitrile, methanol), but loses significant activity at higher solvent concentrations of 30-40 vol%. The enzyme retains high arylsulfotransferase activity in biphasic systems composed of water and nonpolar solvents, such as cyclohexane, toluene and chloroform, while in biphasic systems with more polar solvents (ethyl acetate, 2-pentanone, methyl tert-butyl ether, and butyl acetate) the enzyme activity is completely lost. High yields of AST-catalyzed sulfation were achieved in reactions with several phenols and tyrosine-containing peptides. Overall, AST studied in this work is a promising biocatalyst in organic synthesis to afford efficient sulfation of phenolic compounds under mild reaction conditions.
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PMID:Arylsulfotransferase from Clostridium innocuum-A new enzyme catalyst for sulfation of phenol-containing compounds. 1211 26

Thermal stress is one of the challenges to crop plants that negatively impacts crop yield. To overcome this ever-growing problem, utilization of regulatory mechanisms, especially microRNAs (miRNAs), that provide efficient and precise regulation in a targeted manner have been found to play determining roles. Besides their roles in plant growth and development, many recent studies have shown differential regulation of several miRNAs during abiotic stresses including heat stress (HS). Thus, understanding the underlying mechanism of miRNA-mediated gene expression during HS will enable researchers to exploit this regulatory mechanism to address HS responses. This review focuses on the miRNAs and regulatory networks that were involved in physiological, metabolic and morphological adaptations during HS in plant, specifically in crops. Illustrated examples including, the miR156-SPL, miR169-NF-YA5, miR395-APS/AST, miR396-WRKY, etc., have been discussed in specific relation to the crop plants. Further, we have also discussed the available plant miRNA databases and bioinformatics tools useful for miRNA identification and study of their regulatory role in response to HS. Finally, we have briefly discussed the future prospects about the miRNA-related mechanisms of HS for improving thermotolerance in crop plants.
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PMID:miRNomes involved in imparting thermotolerance to crop plants. 3049 70