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Biochemical Society Transactions Apr 2003This review summarizes the occurrence, properties and role in mucin O-glycosylation pathways of the various members of glycoprotein sulphotransferase families. Although... (Review)
Review
This review summarizes the occurrence, properties and role in mucin O-glycosylation pathways of the various members of glycoprotein sulphotransferase families. Although a number of sulphotransferases have been cloned that act on mucin-type substrates in vitro, it is still difficult to determine exactly which enzymes are responsible for mucin sulphation in vivo. Sulphotransferases play a critical role in determining the chemical, physical and biological properties of mucins. Several of these enzymes have been shown to differ in expression and activity in cancer and inflammation.
Topics: Animals; Humans; Inflammation; Mucins; Neoplasms; Oligosaccharides; Sulfotransferases
PubMed: 12653628
DOI: 10.1042/bst0310318 -
Archives of Ophthalmology (Chicago,... Nov 1997To measure the levels of sulfotransferase activity for keratan sulfate and chondroitin sulfate in serum of patients with macular corneal dystrophy type I, an inherited...
OBJECTIVE
To measure the levels of sulfotransferase activity for keratan sulfate and chondroitin sulfate in serum of patients with macular corneal dystrophy type I, an inherited disorder that is characterized by the absence of sulfate esters on keratan sulfate in the corneal stroma.
METHODS
The amount of sulfur-35 transferred from 3'-phosphoadenosine 5'-phosphosulfate to partially sulfated keratan sulfate and partially sulfated chondroitin sulfate by the sulfotransferase present in serum from patients with macular corneal dystrophy and age-matched controls was determined under conditions where only the added enzyme was rate limiting.
RESULTS
Serum from patients with macular corneal dystrophy type I has the same level of sulfotransferase activity for keratan sulfate and chondroitin sulfate as found in age-matched controls.
CONCLUSIONS
Patients with macular corneal dystrophy type I have sulfotransferase activity for sulfating at least 1 of the 2 sugars in keratan sulfate. It is proposed that the sulfotransferase for N-acetylglucosamine may be deficient.
Topics: Cornea; Corneal Dystrophies, Hereditary; Female; Humans; Male; Sulfotransferases; Carbohydrate Sulfotransferases
PubMed: 9366673
DOI: 10.1001/archopht.1997.01100160589011 -
Tanpakushitsu Kakusan Koso. Protein,... Jul 2001
Review
Topics: Adenosine Diphosphate; Amino Acid Motifs; Amino Acid Sequence; Animals; Binding Sites; Catalysis; Crystallography, X-Ray; Heparitin Sulfate; Humans; Molecular Sequence Data; Protein Conformation; Sequence Alignment; Sulfotransferases
PubMed: 11486371
DOI: No ID Found -
Glycobiology Sep 1999GlcNAc-6-O-sulfotransferase is involved in formation of 6-sulfo-N -acetyllactosamine-containing structures such as 6-sulfo sialyl Lewis x. We investigated the mode of...
GlcNAc-6-O-sulfotransferase is involved in formation of 6-sulfo-N -acetyllactosamine-containing structures such as 6-sulfo sialyl Lewis x. We investigated the mode of expression of GlcNAc-6-O-sulfotransferase during postimplantation embryogenesis in the mouse by in situ hybridization. Sulfotransferase mRNA was not detected on embryonic day (E) 6.5, while on E7.5 it was detected in the mesoderm, ectoderm, and ectoplacental cone. On E10.5, the sulfotransferase signals were mainly observed in the nervous tissue. On E12.5 and 13.5, various tissues in the process of differentiation expressed this mRNA. Several epithelial and mesenchymal tissues undergoing epithelial-mesenchymal interactions strongly expressed the mRNA. For example, in the developing tooth strong sulfotransferase mRNA expression was found only in the condensing mesenchyme on E13.5. On E13.5 and 15.5, the sites showing intense expression of the sulfotransferase again became restricted. In the brain, sulfotransferase mRNA was frequently found as discrete signals in narrow regions. These results suggest that 6-sulfo-N-acetyllactosamine structures have important roles in development. On E13.5 and 15.5, G152 (6-sulfo sialyl Lewis x antigen) was expressed in the neocortex, and AG223 (6-sulfo Lewis x antigen) in the thalamus and neocortex where the sulfotransferase signal was detected. However, in other organs, expression of these antigens did not correlate with the sulfotransferase mRNA, implicating complex nature of regulation of expression of the fucosyl 6-sulfo antigens.
Topics: Animals; Embryo, Mammalian; Gene Expression Regulation, Enzymologic; Lewis Blood Group Antigens; Mice; Mice, Inbred C57BL; Oligosaccharides; Pancreas; RNA, Messenger; Sulfotransferases; Tissue Distribution; Tooth; Carbohydrate Sulfotransferases
PubMed: 10460836
DOI: 10.1093/glycob/9.9.947 -
The Journal of Biological Chemistry Sep 2002We have identified and characterized an N-acetylgalactosamine-4-O-sulfotransferase designated chondroitin-4-sulfotransferase-3 (C4ST-3) (GenBank accession number...
We have identified and characterized an N-acetylgalactosamine-4-O-sulfotransferase designated chondroitin-4-sulfotransferase-3 (C4ST-3) (GenBank accession number AY120869) based on its homology to HNK-1 sulfotransferase (HNK-1 ST). The cDNA predicts an open reading frame encoding a type II membrane protein of 341 amino acids with a 12-amino acid cytoplasmic domain and a 311-amino acid luminal domain containing a single potential N-linked glycosylation site. C4ST-3 has the greatest amino acid sequence identity when aligned with chondroitin-4-O-sulfotransferase 1 (C4ST-1) (45%) but also shows significant amino acid identity with chondroitin-4-O-sulfotransferase 2 (C4ST-2) (27%), dermatan-4-O-sulfotransferase 1 (29%), HNK-1 ST (26%), N-acetylgalactosamine-4-O-sulfotransferase 1 (26%), and N-acetylgalactosamine-4-O-sulfotransferase 2 (23%). C4ST-3 transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is substituted with a beta-linked glucuronic acid at the C-3 hydroxyl. The open reading frame of C4ST-3 is encoded by three exons located on human chromosome 3q21.3. Northern blot analysis reveals a single 2.1-kilobase transcript. C4ST-3 message is expressed in adult liver and at lower levels in adult kidney, lymph nodes, and fetal liver. Although C4ST-3 and C4ST-1 have similar specificities, the highly restricted pattern of expression seen for C4ST-3 suggests that it has a different role than C4ST-1.
Topics: Amino Acid Sequence; Base Sequence; Chromosome Mapping; Cloning, Molecular; DNA, Complementary; Humans; Molecular Sequence Data; Sequence Homology, Amino Acid; Substrate Specificity; Sulfotransferases
PubMed: 12080076
DOI: 10.1074/jbc.M204907200 -
Biochimica Et Biophysica Acta Apr 2000Sulfate residues attached to the specific position of the component sugar residues of glycosaminoglycans play important roles in the formation of functional domain... (Review)
Review
Sulfate residues attached to the specific position of the component sugar residues of glycosaminoglycans play important roles in the formation of functional domain structures. The introduction of a sulfate group is catalyzed by various sulfotransferases with strict substrate specificities. A rapid development achieved in the cloning of various glycosaminoglycan sulfotransferases has allowed us to study the biological functions of glycosaminoglycan sulfotransferases and their products, sulfated glycosaminoglycans.
Topics: Amino Acid Sequence; Animals; Carbohydrate Sequence; Humans; Molecular Sequence Data; Phylogeny; Structure-Activity Relationship; Sulfotransferases
PubMed: 10742590
DOI: 10.1016/s0304-4165(00)00016-7 -
Biochemistry Nov 2002
Review
Topics: Acetylglucosamine; Amino Acid Sequence; Animals; Cytosol; Galactose; Golgi Apparatus; Humans; Molecular Sequence Data; Sulfotransferases; Carbohydrate Sulfotransferases
PubMed: 12403612
DOI: 10.1021/bi020507h -
Genes & Genetic Systems Dec 2019The cytosolic sulfotransferase 1 (SULT1) proteins are a family of highly divergent proteins that show variable expansion in different species during vertebrate...
The cytosolic sulfotransferase 1 (SULT1) proteins are a family of highly divergent proteins that show variable expansion in different species during vertebrate evolution. To clarify the evolutionary origin of the mammalian lineage of the SULT1 family, we compiled Xenopus laevis and X. tropicalis SULT1 (XSULT1) sequences from public databases. The XSULT1 family was found to comprise at least six subfamilies, which corresponded in part to five mammalian SULT1 subfamilies but only poorly to zebrafish SULT1 subfamilies. SULT1C was most highly expanded, and could be divided into at least five subfamilies. A cDNA for X. laevis SULT1B (XlSULT1B.S), a homolog of mammalian SULT1B1, was cloned and its recombinant protein was expressed in a bacterial system. XlSULT1B.S, unlike mammalian SULT1B1, was found to be a monomeric protein of ~34 kDa, and displayed sulfonating activity toward 2-naphthol and p-nitrophenol (pNP). However, we could not detect such sulfonating activity toward any endogenous compounds including thyroid hormones, steroid hormones and dopamine, despite the fact that X. laevis and Rana catesbeiana liver cytosols contained sulfonating activity toward most of these endogenous compounds. At optimum pH (6.4), the Michaelis-Menten constant (K) for pNP was two orders of magnitude greater in XlSULT1B.S (1.04 mM) than in the cytosol preparations (8-15 μM). Our results indicate that Xenopus possesses a prototype of the mammalian SULT1 family, and that XlSULT1B.S showed overall similarities in primary sequence to, and significant differences in molecular and enzymatic properties from, mammalian SULT1B1.
Topics: Animals; Cloning, Molecular; Evolution, Molecular; Female; Humans; Liver; Male; Phylogeny; Rana catesbeiana; Recombinant Proteins; Sequence Analysis, Protein; Species Specificity; Sulfotransferases; Xenopus; Xenopus laevis
PubMed: 31748465
DOI: 10.1266/ggs.19-00026 -
Proceedings of the National Academy of... Apr 2012Heparin is a polysaccharide-based natural product that is used clinically as an anticoagulant drug. Heparan sulfate 3-O-sulfotransferase (3-OST) is an enzyme that...
Heparin is a polysaccharide-based natural product that is used clinically as an anticoagulant drug. Heparan sulfate 3-O-sulfotransferase (3-OST) is an enzyme that transfers a sulfo group to the 3-OH position of a glucosamine unit. 3-OST is present in multiple isoforms, and the polysaccharides modified by these different isoforms perform distinct biological functions. 3-OST isoform 1 (3-OST-1) is the key enzyme for the biosynthesis of anticoagulant heparin. Here, we report the crystal structure of the ternary complex of 3-OST-1, 3'-phosphoadenosine 5'-phosphate, and a heptasaccharide substrate. Comparisons to previously determined structures of 3-OST-3 reveal unique binding modes used by the different isoforms of 3-OST for distinguishing the fine structures of saccharide substrates. Our data demonstrate that the saccharide substrates display distinct conformations when interacting with the different 3-OST isoforms. Site-directed mutagenesis data suggest that several key amino residues, including Lys259, Thr256, and Trp283 in 3-OST-3 and Arg268 in 3-OST-1, play important roles in substrate binding and specificity between isoforms. These results deepen our understanding of the biosynthetic mechanism of heparan sulfate and provide structural information for engineering enzymes for an enhanced biosynthetic approach to heparin production.
Topics: Amino Acid Sequence; Anticoagulants; Heparin; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Sequence Homology, Amino Acid; Substrate Specificity; Sulfotransferases
PubMed: 22431632
DOI: 10.1073/pnas.1117923109 -
Neurotoxicology Jan 2013Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1...
Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds. rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds. In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum. After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus. After 7 days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions. Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level. Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus. rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner. rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections. Induction activity of methamphetamine is in the order of cerebellum>frontal cortex, hippocampus>striatum. These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.
Topics: Animals; Arylsulfotransferase; Blotting, Western; Brain; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Enzyme Induction; Male; Methamphetamine; RNA, Messenger; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sulfotransferases; Time Factors; Transcription, Genetic
PubMed: 23026138
DOI: 10.1016/j.neuro.2012.09.010