Effects of genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by human cytosolic sulfotransferase SULT2A1
| Autor: | Ahsan F. Bairam, Mohammed I. Rasool, Ming-Cheh Liu, Katsuhisa Kurogi, Maryam S. Abunnaja, Masahito Suiko, Fatemah A. Alherz, Amal A. El Daibani, Yoichi Sakakibara, Saud A. Gohal |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Sulfotransferase Dehydroepiandrosterone Single-nucleotide polymorphism medicine.disease_cause Biochemistry Polymorphism Single Nucleotide 03 medical and health sciences Sulfation Affinity chromatography medicine Humans Molecular Biology Escherichia coli Chemistry Mutagenesis Cell Biology Recombinant Proteins Kinetics 030104 developmental biology Pregnenolone Mutagenesis Site-Directed Sulfotransferases medicine.drug |
| Zdroj: | Biochemistry and cell biology = Biochimie et biologie cellulaire. 96(5) |
| ISSN: | 1208-6002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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