sulfate adenylyltransferase


Summary: An enzyme that catalyzes the activation of sulfate ions by ATP to form adenosine-5'-phosphosulfate and pyrophosphate. This reaction constitutes the first enzymatic step in sulfate utilization following the uptake of sulfate. EC

Top Publications

  1. Strott C. Sulfonation and molecular action. Endocr Rev. 2002;23:703-32 pubmed
  2. Schröder E, Gebel L, Eremeev A, Morgner J, Grum D, Knauer S, et al. Human PAPS synthase isoforms are dynamically regulated enzymes with access to nucleus and cytoplasm. PLoS ONE. 2012;7:e29559 pubmed publisher
    ..Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus. ..
  3. Besset S, Vincourt J, Amalric F, Girard J. Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells. FASEB J. 2000;14:345-54 pubmed
    ..Besset, S., Vincourt, J.-B., Amalric, F., Girard, J.-P. Nuclear localization of PAPS synthetase 1: a sulfate activation pathway in the nucleus of eukaryotic cells. ..
  4. Sekulic N, Konrad M, Lavie A. Structural mechanism for substrate inhibition of the adenosine 5'-phosphosulfate kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 and its ramifications for enzyme regulation. J Biol Chem. 2007;282:22112-21 pubmed
    ..Because the ATP-sulfurylase domain of PAPS synthetase influences these elements in the APS kinase domain, we propose that this could be a communication mechanism between the two domains of the bifunctional enzyme. ..
  5. Macrae I, Segel I, Fisher A. Allosteric inhibition via R-state destabilization in ATP sulfurylase from Penicillium chrysogenum. Nat Struct Biol. 2002;9:945-9 pubmed
    ..Disrupting this salt linkage by site-directed mutagenesis induces cooperative inhibition behavior in the absence of an allosteric effector, confirming the role of these two residues. ..
  6. Lalor D, Schnyder T, Saridakis V, Pilloff D, Dong A, Tang H, et al. Structural and functional analysis of a truncated form of Saccharomyces cerevisiae ATP sulfurylase: C-terminal domain essential for oligomer formation but not for activity. Protein Eng. 2003;16:1071-9 pubmed
    ..Careful inspection and modeling revealed that the groove is sufficiently deep and wide, as well as properly positioned, to act as a substrate channel between the ATP sulfurylase and APS kinase-like domains of the enzyme. ..
  7. Gay S, Segel I, Fisher A. Structure of the two-domain hexameric APS kinase from Thiobacillus denitrificans: structural basis for the absence of ATP sulfurylase activity. Acta Crystallogr D Biol Crystallogr. 2009;65:1021-31 pubmed publisher
    ..Therefore, these results provide the first structural insights into a unique hexameric APS kinase that contains a nonfunctional ATP sulfurylase-like domain of unknown function...
  8. MacRae I, Segel I, Fisher A. Crystal structure of ATP sulfurylase from Penicillium chrysogenum: insights into the allosteric regulation of sulfate assimilation. Biochemistry. 2001;40:6795-804 pubmed
    ..This trench may be a vestigial feature of a bifunctional ("PAPS synthetase") ancestor of fungal ATP sulfurylase. ..
  9. Cumming M, Leung S, McCallum J, McManus M. Complex formation between recombinant ATP sulfurylase and APS reductase of Allium cepa (L.). FEBS Lett. 2007;581:4139-47 pubmed
    ..The significance of an interaction between chloroplastidic ATPS and APR in A. cepa is evaluated with respect to the control of the reductive assimilation of sulfate. ..

More Information


  1. Sekulic N, Dietrich K, Paarmann I, Ort S, Konrad M, Lavie A. Elucidation of the active conformation of the APS-kinase domain of human PAPS synthetase 1. J Mol Biol. 2007;367:488-500 pubmed
    ..Both structures reveal extended N termini that approach the active site of the neighboring monomer. Together, these results significantly increase our understandings of how catalysis is achieved by APS-kinase. ..
  2. Li H, Deyrup A, Mensch J, Domowicz M, Konstantinidis A, Schwartz N. The isolation and characterization of cDNA encoding the mouse bifunctional ATP sulfurylase-adenosine 5'-phosphosulfate kinase. J Biol Chem. 1995;270:29453-9 pubmed
    ..Finally, recombinant enzyme expressed in COS-1 cells exhibited both ATP sulfurylase and APS kinase activity. ..
  3. Venkatachalam K, Akita H, Strott C. Molecular cloning, expression, and characterization of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional domains. J Biol Chem. 1998;273:19311-20 pubmed
    ..Purified full-length hPAPSS, in contrast to the COS-1 cell-expressed cDNA construct, exhibited a hyperbolic response curve against ATP suggesting that hPAPSS is perhaps modified in vivo. ..
  4. Murillo M, Leustek T. Adenosine-5'-triphosphate-sulfurylase from Arabidopsis thaliana and Escherichia coli are functionally equivalent but structurally and kinetically divergent: nucleotide sequence of two adenosine-5'-triphosphate-sulfurylase cDNAs from Arabidopsis thali. Arch Biochem Biophys. 1995;323:195-204 pubmed
    ..7 for ATP synthesis. Despite the sequence, structural, and kinetic differences between higher plant and E. coli ATP-sulfurylases, APS2 and APS3 are able to functionally complement E. coli cysD and cysN (ATP-sulfurylase) mutant strains. ..
  5. Kawashima C, Matthewman C, Huang S, Lee B, Yoshimoto N, Koprivova A, et al. Interplay of SLIM1 and miR395 in the regulation of sulfate assimilation in Arabidopsis. Plant J. 2011;66:863-76 pubmed publisher
    ..Thus, miR395 is an integral part of the regulatory circuit controlling plant sulfate assimilation with a complex mechanism of action...
  6. Ullrich T, Blaesse M, Huber R. Crystal structure of ATP sulfurylase from Saccharomyces cerevisiae, a key enzyme in sulfate activation. EMBO J. 2001;20:316-29 pubmed
    ..Despite having similar folds and active site design, examination of the active site of ATPS and comparison with known structures of related nucleotidylyl transferases reveal a novel ATP binding mode that is peculiar to ATP sulfurylases. ..
  7. Hatzfeld Y, Lee S, Lee M, Leustek T, Saito K. Functional characterization of a gene encoding a fourth ATP sulfurylase isoform from Arabidopsis thaliana. Gene. 2000;248:51-8 pubmed
    ..Having identified a fourth plastid-localized ATP sulfurylase, the origin of cytosolic isoform in A. thaliana remains unclear. Based on sequence analysis, it is hypothesized that APS2 may encode the cytosolic ATP sulfurylase. ..
  8. Kurima K, Warman M, Krishnan S, Domowicz M, Krueger R, Deyrup A, et al. A member of a family of sulfate-activating enzymes causes murine brachymorphism. Proc Natl Acad Sci U S A. 1998;95:8681-5 pubmed
    ..We conclude that a family of SK genes are responsible for sulfate activation in mammals, that a mutation in SK2 causes murine brachymorphism, and that members of this gene family have nonredundant, tissue-specific roles. ..
  9. Grum D, van den Boom J, Neumann D, Matena A, Link N, Mueller J. A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex. Biochem Biophys Res Commun. 2010;395:420-5 pubmed publisher
    ..Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells. ..
  10. Karamohamed S, Nilsson J, Nourizad K, Ronaghi M, Pettersson B, Nyren P. Production, purification, and luminometric analysis of recombinant Saccharomyces cerevisiae MET3 adenosine triphosphate sulfurylase expressed in Escherichia coli. Protein Expr Purif. 1999;15:381-8 pubmed
    ..3 kDa). The ATP sulfurylase activity was monitored in real time by a very sensitive bioluminometric method. ..
  11. Liang G, Yang F, Yu D. MicroRNA395 mediates regulation of sulfate accumulation and allocation in Arabidopsis thaliana. Plant J. 2010;62:1046-57 pubmed publisher
    ..Our research showed that miR395 is involved in the regulation of sulfate accumulation and allocation by targeting APS genes and SULTR2;1, respectively...
  12. Girard J, Baekkevold E, Amalric F. Sulfation in high endothelial venules: cloning and expression of the human PAPS synthetase. FASEB J. 1998;12:603-12 pubmed
  13. Hopkins L, Parmar S, Bouranis D, Howarth J, Hawkesford M. Coordinated expression of sulfate uptake and components of the sulfate assimilatory pathway in maize. Plant Biol (Stuttg). 2004;6:408-14 pubmed publisher
    ..In situ hybridization indicated that ZmST1;1 was expressed in epidermal and endodermal cell layers throughout the root whilst OAS(thiol)lyase was highly expressed in the root cortex...
  14. Lansdon E, Fisher A, Segel I. Human 3'-phosphoadenosine 5'-phosphosulfate synthetase (isoform 1, brain): kinetic properties of the adenosine triphosphate sulfurylase and adenosine 5'-phosphosulfate kinase domains. Biochemistry. 2004;43:4356-65 pubmed
    ..Chlorate and perchlorate form dead-end E.MgATP.oxyanion complexes. Phenylalanine, reported to be an inhibitor of brain ATP sulfurylase, was without effect on PAPS synthetase isoform 1. ..
  15. Taguchi Y, Sugishima M, Fukuyama K. Crystal structure of a novel zinc-binding ATP sulfurylase from Thermus thermophilus HB8. Biochemistry. 2004;43:4111-8 pubmed publisher
  16. Patron N, Durnford D, Kopriva S. Sulfate assimilation in eukaryotes: fusions, relocations and lateral transfers. BMC Evol Biol. 2008;8:39 pubmed publisher
  17. Venkatachalam K. Human 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase: biochemistry, molecular biology and genetic deficiency. IUBMB Life. 2003;55:1-11 pubmed
    ..Several single nucleotide polymorphism (SNP) of PAPSS has been identified, some of which are in the coding region (cSNPs), has been shown to have altered enzyme activity. ..
  18. Genevieve D, Heron D, El Ghouzzi V, Prost Squarcioni C, Le Merrer M, Jacquette A, et al. Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation. Eur J Hum Genet. 2005;13:541-6 pubmed
    ..The combination of features observed in the two sisters does not fit with any previously reported SEMD and represents therefore a novel form of autosomal recessive SEMD with MR. ..
  19. Leyh T, Taylor J, Markham G. The sulfate activation locus of Escherichia coli K12: cloning, genetic, and enzymatic characterization. J Biol Chem. 1988;263:2409-16 pubmed
    ..The enzymes of the sulfate activation pathway, ATP sulfurylase (ATP:sulfate adenylyltransferase, EC and APS kinase (ATP:adenosine-5'-phosphosulfate 3'-phosphotransferase, EC 2.7.1...
  20. Xu Z, Freimuth R, Eckloff B, Wieben E, Weinshilboum R. Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) pharmacogenetics: gene resequencing, genetic polymorphisms and functional characterization of variant allozymes. Pharmacogenetics. 2002;12:11-21 pubmed
    ..It will now be possible to test the hypothesis that these common, functionally significant PAPSS2 genetic polymorphisms might contribute to variations in sulfate conjugation in vivo. ..
  21. Bolchi A, Petrucco S, Tenca P, Foroni C, Ottonello S. Coordinate modulation of maize sulfate permease and ATP sulfurylase mRNAs in response to variations in sulfur nutritional status: stereospecific down-regulation by L-cysteine. Plant Mol Biol. 1999;39:527-37 pubmed
  22. Honsel A, Kojima M, Haas R, Frank W, Sakakibara H, Herschbach C, et al. Sulphur limitation and early sulphur deficiency responses in poplar: significance of gene expression, metabolites, and plant hormones. J Exp Bot. 2012;63:1873-93 pubmed publisher
    ..Despite these consequences, the impact of S depletion on growth of poplar plants appears to be less severe than in Brassicaceae such as Arabidopsis thaliana or Brassica sp...
  23. Renosto F, Martin R, Borrell J, Nelson D, Segel I. ATP sulfurylase from trophosome tissue of Riftia pachyptila (hydrothermal vent tube worm). Arch Biochem Biophys. 1991;290:66-78 pubmed
    ATP sulfurylase (ATP: sulfate adenylyltransferase, EC was extensively purified from trophosome tissue of Riftia pachyptila, a tube worm that thrives in deep ocean hydrothermal vent communities...
  24. Ikeda T, Mabuchi A, Fukuda A, Hiraoka H, Kawakami A, Yamamoto S, et al. Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis. J Hum Genet. 2001;46:538-43 pubmed
    ..43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA. ..
  25. Lappartient A, Vidmar J, Leustek T, Glass A, Touraine B. Inter-organ signaling in plants: regulation of ATP sulfurylase and sulfate transporter genes expression in roots mediated by phloem-translocated compound. Plant J. 1999;18:89-95 pubmed
    ..This report presents the first evidence for the regulation of root genes involved in nutrient acquisition and assimilation by a signal that is translocated from shoot to root. ..
  26. Stelzer C, Brimmer A, Hermanns P, Zabel B, Dietz U. Expression profile of Papss2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2) during cartilage formation and skeletal development in the mouse embryo. Dev Dyn. 2007;236:1313-8 pubmed
  27. Shih W, Yu M, Chen P, Wu T, Lin C, Liu C, et al. Evidence for association with hepatocellular carcinoma at the PAPSS1 locus on chromosome 4q25 in a family-based study. Eur J Hum Genet. 2009;17:1250-9 pubmed publisher
    ..These results implicate PAPSS1 as a candidate HCC-susceptibility gene in hepatitis B carriers. ..
  28. Cortes M, Baria A, Schwartz N. Sulfation of chondroitin sulfate proteoglycans is necessary for proper Indian hedgehog signaling in the developing growth plate. Development. 2009;136:1697-706 pubmed publisher
    ..Overall, this study demonstrates an important function for CSPGs in modulating Ihh signaling in the developing growth plate, and highlights the importance of carbohydrate sulfation in regulating growth factor signaling. ..
  29. Vauclare P, Kopriva S, Fell D, Suter M, Sticher L, von Ballmoos P, et al. Flux control of sulphate assimilation in Arabidopsis thaliana: adenosine 5'-phosphosulphate reductase is more susceptible than ATP sulphurylase to negative control by thiols. Plant J. 2002;31:729-40 pubmed
  30. Ullrich T, Huber R. The complex structures of ATP sulfurylase with thiosulfate, ADP and chlorate reveal new insights in inhibitory effects and the catalytic cycle. J Mol Biol. 2001;313:1117-25 pubmed
    ..These new observations are evidence for the crucial role of the displacement mechanism for the catalysis by ATPS. ..
  31. Harjes S, Bayer P, Scheidig A. The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding. J Mol Biol. 2005;347:623-35 pubmed
    ..These observations strongly indicate structural changes during the reaction cycle. Furthermore crystals soaked with ADP and APS could be prepared and the corresponding structures could be solved. ..
  32. Ford Hutchinson A, Ali Z, Seerattan R, Cooper D, Hallgrimsson B, Salo P, et al. Degenerative knee joint disease in mice lacking 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (Papss2) activity: a putative model of human PAPSS2 deficiency-associated arthrosis. Osteoarthritis Cartilage. 2005;13:418-25 pubmed
  33. Bruce J, Ahlquist P, Young J. The host cell sulfonation pathway contributes to retroviral infection at a step coincident with provirus establishment. PLoS Pathog. 2008;4:e1000207 pubmed publisher
  34. Noordam C, Dhir V, McNelis J, Schlereth F, Hanley N, Krone N, et al. Inactivating PAPSS2 mutations in a patient with premature pubarche. N Engl J Med. 2009;360:2310-8 pubmed publisher
    ..These observations indicate that PAPSS2 deficiency is a monogenic adrenocortical cause of androgen excess. ..
  35. Hanna E, Ng K, Macrae I, Bley C, Fisher A, Segel I. Kinetic and stability properties of Penicillium chrysogenum ATP sulfurylase missing the C-terminal regulatory domain. J Biol Chem. 2004;279:4415-24 pubmed
    ..The more negative entropy of activation of the truncated enzyme for APS synthesis is consistent with a role of the C-terminal domain in promoting the effective orientation of MgATP and sulfate at the active site. ..
  36. Dejima K, Seko A, Yamashita K, Gengyo Ando K, Mitani S, Izumikawa T, et al. Essential roles of 3'-phosphoadenosine 5'-phosphosulfate synthase in embryonic and larval development of the nematode Caenorhabditis elegans. J Biol Chem. 2006;281:11431-40 pubmed
    ..elegans. Furthermore, reporter analysis showed that pps-1 is expressed in the epidermis and several gland cells but not in neurons and muscles, indicating that PAPS in the neurons and muscles is provided by other cells. ..
  37. Hesse H, Trachsel N, Suter M, Kopriva S, von Ballmoos P, Rennenberg H, et al. Effect of glucose on assimilatory sulphate reduction in Arabidopsis thaliana roots. J Exp Bot. 2003;54:1701-9 pubmed
    ..Furthermore, signals originating from nitrogen and carbon metabolism regulate APR synergistically...
  38. Yu Z, Lansdon E, Segel I, Fisher A. Crystal structure of the bifunctional ATP sulfurylase-APS kinase from the chemolithotrophic thermophile Aquifex aeolicus. J Mol Biol. 2007;365:732-43 pubmed publisher
    ..This linkage accounts for the low kinase activity of the enzyme under oxidizing conditions. The thermal stability of the Aquifex enzyme can be explained by the 43% decreased cavity volume found within the protein core...
  39. Lyle S, Ozeran J, Stanczak J, Westley J, Schwartz N. Intermediate channeling between ATP sulfurylase and adenosine 5'-phosphosulfate kinase from rat chondrosarcoma. Biochemistry. 1994;33:6822-7 pubmed
    ..These data indicate that APS is channeled between the active sites of ATP sulfurylase and APS kinase during the production of PAPS in rat chondrosarcoma. ..
  40. Beynon J, MacRae I, Huston S, Nelson D, Segel I, Fisher A. Crystal structure of ATP sulfurylase from the bacterial symbiont of the hydrothermal vent tubeworm Riftia pachyptila. Biochemistry. 2001;40:14509-17 pubmed
    ..Amino acid differences between the mobile loops of the enzymes from sulfate assimilators and sulfur chemolithotrophs may account for the significant kinetic differences between the two classes of ATP sulfurylase. ..
  41. van den Boom J, Heider D, Martin S, Pastore A, Mueller J. 3'-Phosphoadenosine 5'-phosphosulfate (PAPS) synthases, naturally fragile enzymes specifically stabilized by nucleotide binding. J Biol Chem. 2012;287:17645-55 pubmed publisher
    ..Moreover, naturally occurring changes in APS concentrations may be sensed by changes in the conformation of PAPSS2. ..
  42. Ramaswamy G, Sohn P, Eberhardt A, Serra R. Altered responsiveness to TGF-? results in reduced Papss2 expression and alterations in the biomechanical properties of mouse articular cartilage. Arthritis Res Ther. 2012;14:R49 pubmed publisher
    ..TGF-? maintains biomechanical properties and regulates expression of Papss2 and sulfation of glycosaminoglycans in mouse articular cartilage. ..
  43. Venkatachalam K, Fuda H, Koonin E, Strott C. Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase. J Biol Chem. 1999;274:2601-4 pubmed
  44. Kurima K, Singh B, Schwartz N. Genomic organization of the mouse and human genes encoding the ATP sulfurylase/adenosine 5'-phosphosulfate kinase isoform SK2. J Biol Chem. 1999;274:33306-12 pubmed
    ..These differences in the two promoter regions suggest that species-specific mechanisms regulate expression of the SK2 isoform. ..
  45. Koprivova A, Melzer M, von Ballmoos P, Mandel T, Brunold C, Kopriva S. Assimilatory sulfate reduction in C(3), C(3)-C(4), and C(4) species of Flaveria. Plant Physiol. 2001;127:543-50 pubmed
  46. Hanna E, Macrae I, Medina D, Fisher A, Segel I. ATP sulfurylase from the hyperthermophilic chemolithotroph Aquifex aeolicus. Arch Biochem Biophys. 2002;406:275-88 pubmed
    ..Consequently, it may also function to produce PAPS for sulfate ester formation or sulfate assimilation when hydrogen serves as the energy source and a reduced inorganic sulfur source is unavailable. ..
  47. Bradley M, Rest J, Li W, Schwartz N. Sulfate activation enzymes: phylogeny and association with pyrophosphatase. J Mol Evol. 2009;68:1-13 pubmed publisher
  48. Franzon V, Gibson M, Hatzinikolas G, Woollatt E, Sutherland G, Cleary E. Molecular cloning of a novel human PAPS synthetase which is differentially expressed in metastatic and non-metastatic colon carcinoma cells. Int J Biochem Cell Biol. 1999;31:613-26 pubmed
    ..1-q23.2. This locus has synteny with the mouse brachymorphic gene recently identified as a PAPS synthetase (SK2). PAPSS2 appears to be the human homologue of this gene and thus PAPSS2 is likely to be important in human skeletogenesis. ..
  49. Liu X, Zhu S, Zou B, Ma Y, Zhou G. [Development of 3-enzyme pyrosequencing system and its application in rapid diagnosis of Down's syndrome]. Yi Chuan. 2010;32:517-23 pubmed
    ..The method is especially suitable to allelic quantification of an SNP, enabling the rapid diagnosis of Down's syndrome by analyzing allele ratio of SNPs on chromosome 21. ..
  50. Mendes Ferreira A, Barbosa C, Jimenez Marti E, del Olmo M, Mendes Faia A. The wine yeast strain-dependent expression of genes implicated in sulfide production in response to nitrogen availability. J Microbiol Biotechnol. 2010;20:1314-21 pubmed
  51. Shirai M, Goto M, Suzuki S, Kono K, Kajiyama T, Kambara H. Highly sensitive pyrosequencing system with polymer-supported enzymes for high-throughput DNA analysis. Anal Chem. 2011;83:7560-5 pubmed publisher
    ..Consequently, the chamber size and bead size immobilizing DNA could be reduced to as small as 6.5 and 4 ?m, respectively. This can be successfully applied to achieving small, inexpensive, pyrosequencing systems with high throughput. ..
  52. Wei J, Leyh T. Conformational change rate-limits GTP hydrolysis: the mechanism of the ATP sulfurylase-GTPase. Biochemistry. 1998;37:17163-9 pubmed
    ..The implications of these finding for GTPase/target interactions and the mechanism of energetic linkage in the ATP sulfurylase system are discussed. ..
  53. Catarzi S, Degl Innocenti D, Iantomasi T, Favilli F, Vincenzini M. The role of H2O2 in the platelet-derived growth factor-induced transcription of the gamma-glutamylcysteine synthetase heavy subunit. Cell Mol Life Sci. 2002;59:1388-94 pubmed
    ..However, for the first time, in S1P-stimulated NIH 3T3 cells, increased levels of GCS-HS mRNA were shown to be related to increases in the reduced glutathione synthesis rate similar to those obtained after PMA and PDGF stimulation. ..