Journal article
Enantioselectivity of human hydroxysteroid sulfotransferase ST2A3 with naphthyl-1-ethanols
Drug metabolism and disposition, Vol.31(6), pp.697-700
2003
DOI: 10.1124/dmd.31.6.697
PMID: 12756199
Abstract
Hydroxysteroid (alcohol) sulfotransferases catalyze the sulfation of several endogenous steroids and many hydrophobic xenobiotic alcohols. The substrate stereoselectivities of sulfotransferases may be critically important in determining their overall roles in metabolism of drugs, carcinogens, and other xenobiotics. In the present work, stereoselectivity of the human hydroxysteroid sulfotransferase ST2A3 (also variously named as SULT2A1 or human DHEA-ST) was examined through analysis of its catalytic activities with the enantiomers of 1-naphthyl-1-ethanol and 2-naphthyl-1ethanol. The kcat/Km value for sulfation of the R-(+)-enantiomer of 1 -naphthyl-1-ethanol catalyzed by ST2A3 was 3.3 min-1mM-1, whereas the S-(-)-enantiomer was not a substrate for the enzyme. S-(-)-1-naphthyl-1-ethanol did however interact with ST2A3 as an inhibitor of the sulfation of dehydroepiandrosterone. This substrate stereospecificity was not present with the enantiomers of 2-naphthyl-1-ethanol, since both were substrates for the enzyme. Such differences between the sulfation of 1- and 2-naphthyl-1-ethanol are consistent with the importance of steric interactions between the ethanol group and a hydrogen atom at the periposition (C8) on the naphthyl ring in 1-naphthyl-1-ethanol that combine with the topology of the enzyme's active site to determine stereospecificity.
Details
- Title: Subtitle
- Enantioselectivity of human hydroxysteroid sulfotransferase ST2A3 with naphthyl-1-ethanols
- Creators
- Jonathan J Sheng - University of IowaMichael W Duffel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Drug metabolism and disposition, Vol.31(6), pp.697-700
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1124/dmd.31.6.697
- PMID
- 12756199
- ISSN
- 0090-9556
- eISSN
- 1521-009X
- Language
- English
- Date published
- 2003
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303160902771
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