Sulfotransferase

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Contents

Function

Sulfotransferase (ST) are enzymes which catalyze the transfer of a sulfate group from a donor molecule to an acceptor alcohol or amine. The acceptors are hormones, neurotransmitters, drugs and xenobiotic compounds. The addition of a charged chemical moiety to the above carbon-rich water-insoluble molecules, make them more soluble and thus transportable in the circulatory system[1]. The various human STs are named SULT1, SULT2, SULT4 and differ in their tissue distribution and substrate specificities. The most common donor molecule is 3’-phosphoadenosine-5’-phosphosulfate (PAP).

  • Estrogen sulfotransferase sulfates estrogen to inactivate it. Involved in sulfation of thyroid hormones[2].
  • Heparan sulphate sulfotransferase sulfates iduronic acid and glucosamine[3].
  • Tyrosylprotein sulfotransferase performs a post translational protein modification by catalysing the transfer of sulphate to Tyr residues[4].
  • Sulfotransferase 1A1, 1A2 are human enzymes which sulfate small planar phenols like neurotransmitters and steroid hormones[5],[6] .
  • Sulfotransferase 1A3 is a human enzyme which sulfates dopamine[7].
  • Sulfotransferase 1C3 is a human enzyme expressed in intestines[8].
  • Sulfotransferase 1E1 is a human enzyme which sulphates ethinyl estradiol[9].
  • Sulfotransferase 2A1 is a human enzyme which sulphates 25-hydroxyvitamin D3[10].
  • Sulfotransferase 2B1, 2B2 are human enzymes which sulphate steroids[11].
  • Sulfotransferase 4A1 is a human enzyme expressed in the brain[12].
  • Sulfotransferase 2A8 is a mouse enzyme which sulphates 7α-hydroxyl bile acid[13].
  • Sulfotransferase STF0 is a microbial enzyme which sulphates trehalose[14].

Relevance

Reduced level of ST expression and activity is observed in liver diseases[15].

Structural highlights

ST catalytic residues His and Lys interact with the sulfate donor molecule PAP[16]. Whole active site. Water molecules are shown as red spheres.

3D structures of sulfotransferase

Sulfotransferase 3D structures

Human estrogen sulfotransferase dimer complex with cofactor PAP, 1hy3

Drag the structure with the mouse to rotate

References

  1. ↑ Malojcic G, Glockshuber R. The PAPS-independent aryl sulfotransferase and the alternative disulfide bond formation system in pathogenic bacteria. Antioxid Redox Signal. 2010 Oct;13(8):1247-59. doi: 10.1089/ars.2010.3119. PMID:20136513 doi:http://dx.doi.org/10.1089/ars.2010.3119
  2. ↑ Yi M, Negishi M, Lee SJ. Estrogen Sulfotransferase (SULT1E1): Its Molecular Regulation, Polymorphisms, and Clinical Perspectives. J Pers Med. 2021 Mar 11;11(3):194. PMID:33799763 doi:10.3390/jpm11030194
  3. ↑ Teixeira FCOB, Vijaya Kumar A, Kumar Katakam S, Cocola C, Pelucchi P, Graf M, Kiesel L, Reinbold R, Pavão MSG, Greve B, Götte M. The Heparan Sulfate Sulfotransferases HS2ST1 and HS3ST2 Are Novel Regulators of Breast Cancer Stem-Cell Properties. Front Cell Dev Biol. 2020 Sep 25;8:559554. PMID:33102470 doi:10.3389/fcell.2020.559554
  4. ↑ Ouyang Yb, Lane WS, Moore KL. Tyrosylprotein sulfotransferase: purification and molecular cloning of an enzyme that catalyzes tyrosine O-sulfation, a common posttranslational modification of eukaryotic proteins. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2896-901. PMID:9501187 doi:10.1073/pnas.95.6.2896
  5. ↑ Nagar S, Walther S, Blanchard RL. Sulfotransferase (SULT) 1A1 polymorphic variants *1, *2, and *3 are associated with altered enzymatic activity, cellular phenotype, and protein degradation. Mol Pharmacol. 2006 Jun;69(6):2084-92. PMID:16517757 doi:10.1124/mol.105.019240
  6. ↑ Engelke CE, Meinl W, Boeing H, Glatt H. Association between functional genetic polymorphisms of human sulfotransferases 1A1 and 1A2. Pharmacogenetics. 2000 Mar;10(2):163-9. PMID:10762004 doi:10.1097/00008571-200003000-00008
  7. ↑ Bian HS, Ngo SY, Tan W, Wong CH, Boelsterli UA, Tan TM. Induction of human sulfotransferase 1A3 (SULT1A3) by glucocorticoids. Life Sci. 2007 Dec 14;81(25-26):1659-67. PMID:17963788 doi:10.1016/j.lfs.2007.09.029
  8. ↑ Dubaisi S, Fang H, Kocarek TA, Runge-Morris M. Transcriptional Regulation of Human Cytosolic Sulfotransferase 1C3 by Peroxisome Proliferator-Activated Receptor γ in LS180 Human Colorectal Adenocarcinoma Cells. Mol Pharmacol. 2016 Nov;90(5):562-569. PMID:27565680 doi:10.1124/mol.116.106005
  9. ↑ Schrag ML, Cui D, Rushmore TH, Shou M, Ma B, Rodrigues AD. Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl estradiol. Drug Metab Dispos. 2004 Nov;32(11):1299-303. PMID:15483196 doi:10.1124/dmd.32.11
  10. ↑ Wong T, Wang Z, Chapron BD, Suzuki M, Claw KG, Gao C, Foti RS, Prasad B, Chapron A, Calamia J, Chaudhry A, Schuetz EG, Horst RL, Mao Q, de Boer IH, Thornton TA, Thummel KE. Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D(3)-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans. Drug Metab Dispos. 2018 Apr;46(4):367-379. PMID:29343609 doi:10.1124/dmd.117.078428
  11. ↑ Falany CN, He D, Dumas N, Frost AR, Falany JL. Human cytosolic sulfotransferase 2B1: isoform expression, tissue specificity and subcellular localization. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):214-21. PMID:17055258 doi:10.1016/j.jsbmb.2006.09.011
  12. ↑ Minchin RF, Lewis A, Mitchell D, Kadlubar FF, McManus ME. Sulfotransferase 4A1. Int J Biochem Cell Biol. 2008;40(12):2686-91. PMID:18248844 doi:10.1016/j.biocel.2007.11.010
  13. ↑ Teramoto T, Nishio T, Kurogi K, Sakakibara Y, Kakuta Y. The crystal structure of mouse SULT2A8 reveals the mechanism of 7alpha-hydroxyl, bile acid sulfation. Biochem Biophys Res Commun. 2021 May 21;562:15-20. doi:, 10.1016/j.bbrc.2021.04.113. PMID:34030040 doi:http://dx.doi.org/10.1016/j.bbrc.2021.04.113
  14. ↑ Paul P, Suwan J, Liu J, Dordick JS, Linhardt RJ. Recent advances in sulfotransferase enzyme activity assays. Anal Bioanal Chem. 2012 Jun;403(6):1491-500. PMID:22526635 doi:10.1007/s00216-012-5944-4
  15. ↑ Yalcin EB, More V, Neira KL, Lu ZJ, Cherrington NJ, Slitt AL, King RS. Downregulation of sulfotransferase expression and activity in diseased human livers. Drug Metab Dispos. 2013 Sep;41(9):1642-50. doi: 10.1124/dmd.113.050930. Epub 2013, Jun 17. PMID:23775849 doi:http://dx.doi.org/10.1124/dmd.113.050930
  16. ↑ Pedersen LC, Petrotchenko E, Shevtsov S, Negishi M. Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction. J Biol Chem. 2002 May 17;277(20):17928-32. Epub 2002 Mar 7. PMID:11884392 doi:http://dx.doi.org/10.1074/jbc.M111651200

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