Disease relevance of phosphoadenosine phosphosulfate

• Three different cDNAs, Prh-19, Prh-26, and Prh-43 [3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase homolog], have been isolated by complementation of an Escherichia coli cysH mutant, defective in PAPS reductase activity, to prototrophy with an Arabidopsis thaliana cDNA library in the expression vector lambda YES [1].
• Six primary and 10 secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons were tested for mutagenicity in Salmonella typhimurium TA98 in the presence of varying amounts of hepatic cytosol from adult male and female rats and 3'-phosphoadenosine-5'-phosphosulfate, the cofactor for sulfotransferases [2].
• Both sulfurylase and kinase from rat chondrosarcoma were copurified through substrate affinity chromatography using stable analogs of APS (adenosine 5'-phosphosulfate) and PAPS (3'-phosphoadenosine 5'-phosphosulfate) [3].
• Sinorhizobium sp. strain BR816 possesses two nodPQ copies, providing activated sulfate (3'-phosphoadenosine-5'-phosphosulfate [PAPS]) needed for the biosynthesis of sulfated Nod factors [4].
• Crude extracts of Rhodospirillum rubrum catalyzed the formation of acid-volatile radioactivity from (35S) sulfate, (35S) adenosine-5'-phosphosulfate, and (35S) 3'-phosphoadenosine-5'-phosphosulfate [5].

High impact information on phosphoadenosine phosphosulfate

• Sulfohydrolase activity toward 3'-phosphoadenosine-5'-phosphosulfate was higher in fetal and newborn livers and in placentas than in adult liver [6].
• We sequenced candidate genes from the region and identified a missense mutation in the chondroitin 6-O-sulfotransferase (C6ST-1) gene (CHST3) changing an arginine into a glutamine (R304Q) in the well conserved 3'-phosphoadenosine 5'-phosphosulfate binding site [7].
• This activation is direct and appears to extend to other xenobiotic sulfotransferases as well as to 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2), an enzyme that generates the donor cofactor for the reaction [8].
• A missense mutation in the SK2 coding sequence of bm mice that alters a highly conserved amino acid residue destroys adenosine-phosphosulfate kinase activity and therefore the ability of SK2 to synthesize PAPS [9].
• This reaction is mediated by a Golgi enzyme activity called tyrosylprotein sulfotransferase (TPST) that catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to tyrosine residues within acidic motifs of polypeptides [10].

Chemical compound and disease context of phosphoadenosine phosphosulfate

• Cloning of the 3'-phosphoadenylyl sulfate reductase and sulfite reductase genes from Escherichia coli K-12 [11].
• The elimination of extracellular calcium or treatment with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, suramin, or adenosine-3'-phosphate-5'-phosphosulfate did not inhibit ATP- or ADP-induced membrane ruffling, whereas AR-C69931MX or pertussis toxin treatments clearly did so [12].

Biological context of phosphoadenosine phosphosulfate

• The GXXGXXK motif forms the active binding site for the universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate [13].
• NMHEA-induced alkylation was also studied in male and female brachymorphic mice, which are deficient in the ability to synthesize the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate required for sulfotransferase activity, and their heterozygous siblings [14].
• The results of substrate interaction kinetics and product inhibition are consistent with an Ordered Bi Bi mechanism where 3'-phosphoadenosine 5'-phosphosulfate is the first substrate to bind to the enzyme and 3'-phosphoadenosine 5'-phosphate is the final product to be released [15].
• The enzyme shows sequence homology to the sulfotransferases and requires 3'-phosphoadenosine 5'-phosphosulfate for activity [16].
• The comparison of the deduced amino acid sequences of plant and animal sulfotransferases (ST) has allowed the identification of four well conserved regions, and previous experimental evidence suggested that regions I and IV might be involved in the binding of the cosubstrate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) [17].

Anatomical context of phosphoadenosine phosphosulfate

• Hepatic cytosols catalyzed a 3'-phosphoadenosine 5'-phosphosulfate (PAPS)-dependent O-sulfonation of N-hydroxy-N-methyl-4-aminoazobenzene (N-HO-MAB) and of several other N-hydroxy arylamines [18].
• The unlabeled microsomes provide "HSact conversion activity" that requires 3'-phosphoadenosine 5'-phosphosulfate to convert [35S]HSPGinact into [35S] HSPGact, presumably by sulfation [19].
• Microsomal preparations from cultured chick embryo chondrocytes were incubated with 3'-phosphoadenosine 5'-phosphosulfate and oligosaccharides prepared from chondroitin [20].
• Assay of UDP-galactose-ceramide galactosyltransferase, 3'-phosphoadenosine 5'-phosphosulfate galactosylceramide sulfotransferase, and 2',3'-cyclic nucleotide 3'-phosphohydrolase activities showed that the levels of these enzymes were 446, 76, and 11 times lower, respectively, than the levels measured in mature oligodendrocytes [21].
• In addition, cytosol prepared from oocytes was tested for iodothyronine sulfotransferase activity by incubation of 1 mg cytosolic protein/ml for 30 min at 21 C with 1 microM [125I]T4, [125I]T3, [125I]rT3, or [125I]3,3'-T2 and 50 microM 3'-phosphoadenosine-5'-phosphosulfate [22].

Associations of phosphoadenosine phosphosulfate with other chemical compounds

• With cytosol, 3'-phosphoadenosine-5'-phosphosulfate and dopamine Km values were 17.2 +/- 4.1 and 22.4 +/- 3.5 microM [23].
• When alpha-hydroxytamoxifen (alpha-OHTAM) was incubated with rat liver hydroxysteroid (alcohol) sulfotransferase a (STa) and 3'-phosphoadenosine 5'-phosphosulfate, (E)-alpha-OHTAM was found to be a better substrate for STa than (Z)-alpha-OHTAM [24].
• 1'-Hydroxysafrole was metabolized at a low rate by rat and mouse liver cytosols in a 3'-phosphoadenosine 5'-phosphosulfate-dependent reaction to a derivative (presumably the sulfuric acid ester) that was captured by its reaction with RNA [25].
• Tyrosine O-sulfation, a common post-translational modification in eukaryotes, is mediated by Golgi enzymes that catalyze the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate to tyrosine residues in polypeptides [26].
• In steroid biosynthesis, human dehydroepiandrosterone sulfotransferase (DHEA-ST) in the adrenals has been reported to catalyze the transfer of the sulfonate group from 3'-phosphoadenosine-5'-phosphosulfate to dehydroepiandrosterone (DHEA) [27].

Gene context of phosphoadenosine phosphosulfate

• Inhibition of M and P phenol sulfotransferase by analogues of 3'-phosphoadenosine-5'-phosphosulfate [28].
• Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) pharmacogenetics: gene resequencing, genetic polymorphisms and functional characterization of variant allozymes [29].
• In addition, ST1C2 did not mediate 3'-phosphoadenosine-5'-phosphosulfate-dependent DNA binding of N-OH-AAF [30].
• Pharmacogenetics of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1): gene resequencing, sequence variation, and functional genomics [31].
• These reactions are catalyzed by an expanding family of sulfotransferase (SULT) enzymes, which transfer a sulfuryl moiety from the universal donor 3'-phosphoadenosine 5'-phosphosulfate [32].

Analytical, diagnostic and therapeutic context of phosphoadenosine phosphosulfate

• Molecular cloning and identification of 3'-phosphoadenosine 5'-phosphosulfate transporter [33].
• Using sequence alignments with other carbohydrate and cytosolic sulfotransferases, we selected residues within the putative binding regions for 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the carbohydrate substrate for mutagenesis [34].
• Expression, purification and crystallization of human 3'-phosphoadenosine-5'-phosphosulfate synthetase 1 [35].
• An assay method for ATP-sulfurylase is described, based on the incorporation of 35SO4(2-) into adenosine-5'-phosphosulfate (and 3-phosphoadenosine-5'-phosphosulfate) and the separation of these compounds by HPLC [36].
• The activity of 3'-phosphoadenosine 5'-phosphosulfate reductase, the key enzyme of the assimilatory sulfate reduction pathway in fungi, was increased by sulfur starvation and decreased after treatment with glutathione revealing an uncoupling of sulfate uptake and reduction in the presence of reduced sulfur compounds [37].

References