2. Academic Validation
  3. Effects of genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by human cytosolic sulfotransferase SULT2A1

Effects of genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by human cytosolic sulfotransferase SULT2A1

  • Biochem Cell Biol. 2018 Oct;96(5):655-662. doi: 10.1139/bcb-2017-0341.
Maryam S Abunnaja 1,  Fatemah A Alherz 1,  Amal A El Daibani 1,  Ahsan F Bairam 1 2,  Mohammed I Rasool 1 3,  Saud A Gohal 1,  Katsuhisa Kurogi 1 4,  Masahito Suiko 4,  Yoichi Sakakibara 4,  Ming-Cheh Liu 1
Affiliations

Affiliations

  • 1 a Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614, USA.
  • 2 b Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq.
  • 3 c Department of Pharmacology, College of Pharmacy, University of Karbala, Karbala, Iraq.
  • 4 d Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki 889-2192 Japan.
PMID: 29671343 DOI: 10.1139/bcb-2017-0341
Abstract

The cytosolic sulfotransferase (SULT) SULT2A1 is known to mediate the sulfation of DHEA as well as some other hydroxysteroids such as pregnenolone. The present study was designed to investigate how genetic polymorphisms of the human SULT2A1 gene may affect the sulfation of DHEA and pregnenolone. Online databases were systematically searched to identify human SULT2A1 single nucleotide polymorphisms (SNPs). Of the 98 SULT2A1 non-synonymous coding SNPs identified, seven were selected for further investigation. Site-directed mutagenesis was used to generate cDNAs encoding these seven SULT2A1 allozymes, which were expressed in BL21 Escherichia coli cells and purified by glutathione-Sepharose affinity chromatography. Enzymatic assays revealed that purified SULT2A1 allozymes displayed differential sulfating activity toward both DHEA and pregnenolone. Kinetic analyses showed further differential catalytic efficiency and substrate affinity of the SULT2A1 allozymes, in comparison with wild-type SULT2A1. These findings provided useful information concerning the effects of genetic polymorphisms on the sulfating activity of SULT2A1 allozymes.

Keywords

DHEA; SULT; SULT2A1; cytosolic sulfotransferase; dehydroepiandrosterone; déhydroépiandrostérone; polymorphismes mononucléotidiques; pregnenolone; prégnénolone; single nucleotide polymorphisms; sulfatation; sulfation; sulfotransférase cytosolique.

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