Sulfotransferases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility

Chapman, Eli; Best, Michael D.; Hanson, Sarah R.; Wong, Chi Huey

doi:10.1002/anie.200300631

Cited by 349 publications

(217 citation statements)

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“…Sulfotransferases (SULTs) are one of the major superfamily of phase II drug metabolizing enzymes (Bojarova and Williams, 2008;Chapman et al, 2004;Gamage et al, 2006;Hempel et al, 2007;Kauffman, 2004;Rath et al, 2004;Runge-Morris and Kocarek, 2005;Wang and James, 2006). They catalyze the sulfation of hydroxyl-containing compounds.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Zhou¹

2010

American Journal of Pharmacology and Toxicology

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Problem statement: Sulfotransferases (SULTs) are important phase II drug metabolizing enzymes. They also regulate the biological activities of various hormones. To the best of our knowledge, psychostimulants regulation of SULTs is basically not studied except one article reported that Methamphetamine (METH) treatment induced rat amygdale rSULT1A1 mRNA 4.3 fold by using microarray method to identify a series of candidate genes after single-dose METH treatment. The psychostimulant METH is used to treat disorders such as attention deficit, narcolepsy and obesity. It is also a highly addictive drug that causes serious social problems. The abuse of this drug leads to the damage of monoaminergic systems in the mammalian brain. It is important to understand how SULT expressions are regulated by psychostimulants. Approach: This study was performed to evaluate the effect of METH on SULT gene expressions in rat liver and brain. METH (0, 1, 5, 20 mg kg −1 day −1 ) was used to treat male and female rats for 7 days by oral administration. Rat livers and brains were collected 24 h after the final drug treatment. Western blot and real-time RT-PCR were used to investigate the effect of METH on SULT protein and mRNA expression, respectively, in rat liver and brain. Results: Proteins and mRNAs of rSULT1A1, rSULT2A1 and rSULT1E1 were induced in liver and brain of both male and female rats following METH treatment. rSULT1E1 was induced at much higher level compared to that of rSULT1A1 and rSULT2A1. Brain inductions were found to be much higher than those found in liver. Conclusion: These data suggest an important role of the central dopaminergic system in the regulation of liver and brain rSULT expressions.

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Section: Introductionmentioning

confidence: 99%

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Zhou¹

2010

American Journal of Pharmacology and Toxicology

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“…The prediction of an ST within a PKS was unprecedented (4). STs are widely distributed and are known to have detoxification, hormone regulation, or signaling functions (10). They catalyze transfer of a sulfonate group from the donor PAPS to a hydroxyl or amine of an acceptor small molecule or protein.…”

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confidence: 99%

Terminal Alkene Formation by the Thioesterase of Curacin A Biosynthesis

Gehret

Gerwick

et al. 2011

Journal of Biological Chemistry

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Curacin A is a polyketide synthase (PKS)-non-ribosomal peptide synthetase-derived natural product with potent anticancer properties generated by the marine cyanobacterium Lyngbya majuscula. Type I modular PKS assembly lines typically employ a thioesterase (TE) domain to off-load carboxylic acid or macrolactone products from an adjacent acyl carrier protein (ACP) domain. In a striking departure from this scheme the curacin A PKS employs tandem sulfotransferase and TE domains to form a terminal alkene moiety. Sulfotransferase sulfonation of ␤-hydroxy-acyl-ACP is followed by TE hydrolysis, decarboxylation, and sulfate elimination (Gu, L., Wang, B., Kulkarni, A., Gehret, J. J., Lloyd, K. R., Gerwick, L., Gerwick, W. H., Wipf, P.

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“…Sulfotransferases (SULTs) 3 are phase II drug-metabolizing enzymes that catalyze the sulfation (sulfonation) of various hydroxyl-containing compounds: biosignaling molecules such as hydroxysteroid hormones, thyroid hormones, glucocorticoid hormones, bile acids, neurotransmitters, and hydroxylcontaining xenobiotics (1)(2)(3)(4)(5)(6)(7)(8). The sulfation proceeds as shown in reaction 1, where the sulfuryl group donor is adenosine 3Ј-phosphate 5Ј-phosphosulfate (PAPS), and the reaction products are adenosine 3Ј,5Ј-diphosphate (PAP) and a sulfated product.…”

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confidence: 99%

para-Nitrophenyl Sulfate Activation of Human Sulfotransferase 1A1 Is Consistent with Intercepting the E·PAP Complex and Reformation of E·PAPS

Tyapochkin

Cook

Chen

2009

Journal of Biological Chemistry

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Cytosolic sulfotransferase (SULT)-catalyzed sulfation regulates biological activities of various biosignaling molecules and metabolizes hydroxyl-containing drugs and xenobiotics. The universal sulfuryl group donor for SULT-catalyzed sulfation is adenosine 3-phosphate 5-phosphosulfate (PAPS), whereas the reaction products are a sulfated product and adenosine 3,5-diphosphate (PAP). Although SULT-catalyzed kinetic mechanisms have been studied since the 1980s, they remain unclear. Human SULT1A1 is an important phase II drug-metabolizing enzyme. Previously, isotope exchange at equilibrium indicated steady-state ordered mechanism with PAPS and PAP binding to the free SULT1A1 (Tyapochkin, E., Cook, P. F., and Chen, G. Sulfotransferases (SULTs)3 are phase II drug-metabolizing enzymes that catalyze the sulfation (sulfonation) of various hydroxyl-containing compounds: biosignaling molecules such as hydroxysteroid hormones, thyroid hormones, glucocorticoid hormones, bile acids, neurotransmitters, and hydroxylcontaining xenobiotics (1-8). The sulfation proceeds as shown in reaction 1, where the sulfuryl group donor is adenosine 3Ј-phosphate 5Ј-phosphosulfate (PAPS), and the reaction products are adenosine 3Ј,5Ј-diphosphate (PAP) and a sulfated product. R-OH ϩ PAPS L | ;One of the main biological functions of SULTs is the regulation of various hormones (9). Sulfation of xenobiotics is mainly associated with detoxification, biotransformation of a relatively hydrophobic xenobiotic into a more water-soluble sulfuric ester that is readily excreted. However, in some cases sulfation can also cause bioactivation of procarcinogens and promutagens, leading to possible toxic effects (10, 11).Studies of the SULTs kinetic mechanisms began to appear in the early 1980s (12). Although many SULT isoforms have been isolated and characterized, their biological functions and catalytic mechanisms are still not well understood. Human phenol sulfotransferase (SULT1A1) is one of the major detoxifying enzymes for phenolic xenobiotics; it also catalyzes the sulfation of endogenous hydroxyl biosignaling molecules. It has very broad substrate specificity and high activity toward most phenolic compounds. SULT1A1 is also widely distributed in the human body. On the basis of isotope exchange at equilibrium, we showed that the kinetic mechanism for human SULT1A1 is steady-state-ordered with PAPS binding to the protein first, and PAP released last (13).Substrate inhibition by the hydroxyl substrate (sulfate acceptor) is a common feature of most cytosolic SULTs (14,15). Inhibition of SULT1A1 has been observed by the substrate, naphthol. There are a number of different mechanisms that have been proposed for substrate inhibition, but the mechanism remains unclear. A ternary complex formed between substrate and the enzyme⅐PAP complex is the most likely possibility in an ordered mechanism, but binding to free enzyme is also possible (12,16). It is also possible, but unlikely, that substrate could bind to central complexes. In addition, binding of two substrate...

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Sulfotransferases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility

Cited by 349 publications

References 472 publications

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Terminal Alkene Formation by the Thioesterase of Curacin A Biosynthesis

para-Nitrophenyl Sulfate Activation of Human Sulfotransferase 1A1 Is Consistent with Intercepting the E·PAP Complex and Reformation of E·PAPS

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