Inhibition and Binding Studies of Coenzyme A and Bovine Phenol Sulfotransferase

Leach, Michael; Cameron, Elizabeth A.; Fite, Nathan C.; Stassinopoulos, Jerry; Palmreuter, Neal; Beckmann, Joe D.

doi:10.1006/bbrc.1999.1096

Cited by 11 publications

(12 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some caution is warranted as we look back on work performed with partially purified nonrecombinant enzymes; however, all reports provide a consistent picture that PAPS can bind to the enzyme in the absence of a phenol. This is supported by the frequent use of nucleotide agaroses for affinity purification (16,17), by the presence of PAP found tightly bound to a recombinant rat enzyme (9), and by recent crystallization of mouse estrogen sulfotransferase complexes with PAP and PAPS (18).…”

mentioning

confidence: 95%

“…Exogenous inhibitors include polyphenolic compounds (20,21), aryl carboxylic acids (22), aryl aldehydes (23), and polyhalogenated phenols (13,24). Endogenous inhibitors include ATP (14,15), pyridoxal phosphate (25), and CoA (17). The latter is of interest due to its overt structural overlap with PAP, another potent sulfotransferase inhibitor (26) generated by normal enzymatic turnover.…”

mentioning

confidence: 99%

“…The latter is of interest due to its overt structural overlap with PAP, another potent sulfotransferase inhibitor (26) generated by normal enzymatic turnover. CoA was found to be a competitive inhibitor with respect to PAPS of the bovine phenol sulfotransferase (bSULT1A1) (17), an enzyme with very similar sequence and substrate specificity compared with the human SULT1A1 enzyme (27).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Bovine Phenol Sulfotransferase (bSULT1A1) by CoA Thioesters

Tulik

Chodavarapu

Edgar

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Previous work with the bovine phenol sulfotransferase (bSULT1A1, EC ) demonstrated inhibition by CoA that was competitive with respect to the sulfuryl donor substrate, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) (Leach, M., Cameron, E., Fite, N., Stassinopoulos, J., Palmreuter, N., and Beckmann, J. D. (1999) Biochem. Biophys. Res. Commun. 261, 815-819). Here we report that long chain acyl-CoAs are more potent inhibitors of bSULT1A1 and also of human dopamine sulfotransferase (SULT1A3) when compared with unesterified CoA and short chain-length acyl-CoAs. A complex pattern of inhibition was revealed by systematic variation of palmitoyl-CoA, PAPS, and 7-hydroxycoumarin, the acceptor substrate. Convex plots of apparent K(m)/V(max) versus [palmitoyl-CoA] were adequately modeled using an ordered rapid equilibrium scheme with PAPS as the leading substrate and by accounting for the possible binding of two equivalents of inhibitor to the dimeric enzyme. Interestingly, the first K(i) of 2-3 microm was followed by a second K(i) of only 0.01-0.05 microm, suggesting that positive subunit cooperativity enhances binding of long chain acyl-CoAs to this sulfotransferase. Simultaneous interaction of palmitoyl-CoA with both the nucleotide and phenol binding sites is suggested by two experiments. First, the acyl-CoA displaced 7-hydroxycoumarin from the highly fluorescent bSULT1A1.PAP.7-HC complex in a cooperative manner. Second, palmitoyl-CoA prevented the quenching of bSULT1A1 fluorescence observed with pentachlorophenol. Finally, titrations of bSULT1A1-pentachlorophenol complex with palmitoyl-CoA caused the return of protein fluorescence, and the binding of palmitoyl-CoA was highly cooperative (Hill constant of 1.9). Overall, these results suggest a model of sulfotransferase inhibition in which the 3'-phosphoadenosine-5'-diphosphate moiety of CoA docks to the PAPS domain, and the acyl-pantetheine group docks to the hydrophobic phenol binding domain.

show abstract

mentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Bovine Phenol Sulfotransferase (bSULT1A1) by CoA Thioesters

Tulik

Chodavarapu

Edgar

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…ATP is a dead-end inhibitor of human phenol SULT with a reported K i of 170 μM [9]. Coenzyme A can also inhibit bovine phenol SULT with a K i of 1.3 μM [11]. Coenzyme A can also inhibit bovine phenol SULT with a K i of 1.3 μM [11].…”

Section: Discussionmentioning

confidence: 99%

“…A number of non-steroidal anti-inflammatory drugs are shown to inhibit phenol SULTs. In addition to xenobiotics, some endogenous compounds such as ATP [9], pyridoxal phosphate [10] and coenzyme A [11] could inhibit phenol SULTs. Other drugs such as nimesulide, meclofenamate and piroxicam are also selective towards hSULT1A1 inhibition, whereas sulindac and ibuprofen exhibit more selective inhibitory effects on hSULT1E1 (ST1E4) sulfation [8].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of kynurenic acid, a tryptophan metabolite, and its derivatives on cytosolic sulfotransferases

Senggunprai

Yoshinari

Yamazoe

2009

Biochemical Journal

View full text Add to dashboard Cite

KYNA (kynurenic acid) is an endogenous metabolite of tryptophan in the kynurenine pathway and has been characterized as an antagonist of ionotropic glutamate receptors. In addition, we have reported this endogenous compound as a potent inhibitor of SULTs (cytosolic sulfotransferases). In the present study we characterized the inhibitory effects of KYNA on several human (h) and mouse (m) recombinant SULTs. No sulfate metabolite of KYNA was detected with mouse and human SULTs examined under the conditions used, suggesting that it is a bona fide inhibitor of SULTs. Among the mouse enzymes examined, KYNA exhibited selective inhibitory effects on Sult1b1-mediated sulfation of various compounds with IC50 values in the low micromolar range (2.9-4.9 microM). KYNA also exerted an inhibitory activity towards hSULT1A1 and hSULT1B1. The inhibitory potency of KYNA for mSult1b1 was stronger than that of 2,6-dichloro-4-nitrophenol, a known non-specific SULT inhibitor, whereas the potencies of these two inhibitors for hSULT1B1 were comparable. The inhibitory characteristics of KYNA were clearly distinct from those of mefenamic acid, a selective inhibitor of SULT1A enzymes. The KYNA derivatives 5,7-dichlorokynurenic acid and L689,560 exhibited preferential inhibitory effects on hSULT1A1 and hSULT1B1 respectively. Interestingly, gavestinel, another KYNA derivative, was found to be an extremely potent inhibitor of hSULT1B1. Finally, we have demonstrated that the mechanism underlying the KYNA inhibition varied depending on the enzyme and substrate involved. Taken together, the present results unveil another distinct aspect of KYNA and its derivatives as an inhibitor of SULTs.

show abstract

Homology modeling and PAPS ligand (cofactor) binding study of bovine phenol sulfotransferase

Zheng

Xiao

et al. 2005

J Mol Model

View full text Add to dashboard Cite

In order to understand the mechanisms of ligand binding and the interaction between the ligand and the bovine phenol sulfotransferase, (bSULT1A1, EC 2.8.2.1) a three-dimensional (3D) model of the bSULT1A1 is generated based on the crystal structure of the estrogen sulfotransferase (PDB code 1AQU) by using the InsightII/Homology module. With the aid of the molecular mechanics and molecular dynamics methods, the final refined model is obtained and is further assessed by Profile-3D and ProStat, which show that the refined model is reliable. With this model, a flexible docking study is performed and the results indicate that 3'-phosphoadenosine-5'- phosphosulfate (PAPS) is a more preferred ligand than coenzyme A (CoA), and that His108 forms hydrogen bond with PAPS, which is in good agreement with the experimental results. From these docking studies, we also suggest that Phe255, Phe24 and Tyr169 in bSULT1A1 are three important determinant residues in binding as they have strong van-der-Waals contacts with the ligand. The hydrogen-bonding interactions also play an important role for the stability of the complex. Our results may be helpful for further experimental investigations.

show abstract

Inhibition and Binding Studies of Coenzyme A and Bovine Phenol Sulfotransferase

Cited by 11 publications

References 16 publications

Inhibition of Bovine Phenol Sulfotransferase (bSULT1A1) by CoA Thioesters

Inhibition of Bovine Phenol Sulfotransferase (bSULT1A1) by CoA Thioesters

Inhibitory effects of kynurenic acid, a tryptophan metabolite, and its derivatives on cytosolic sulfotransferases

Homology modeling and PAPS ligand (cofactor) binding study of bovine phenol sulfotransferase

Contact Info

Product

Resources

About