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

被引：7

作者：

Abunnaja, Maryam S. ^{[1
]}

Alherz, Fatemah A. ^{[1
]}

El Daibani, Amal A. ^{[1
]}

Bairam, Ahsan F. ^{[1
,2
]}

Rasool, Mohammed, I ^{[1
,3
]}

Gohal, Saud A. ^{[1
]}

Kurogi, Katsuhisa ^{[1
,4
]}

Suiko, Masahito ^{[4
]}

Sakakibara, Yoichi ^{[4
]}

Liu, Ming-Cheh ^{[1
]}

机构：

[1] Univ Toledo, Dept Pharmacol, Coll Pharm & Pharmaceut Sci, Hlth Sci Campus, Toledo, OH 43614 USA

[2] Univ Kufa, Coll Pharm, Dept Pharmacol, Najaf, Iraq

[3] Univ Karbala, Coll Pharm, Dept Pharmacol, Karbala, Iraq

[4] Univ Miyazaki, Biochem & Appl Biosci, Miyazaki 8892192, Japan

来源：

BIOCHEMISTRY AND CELL BIOLOGY | 2018年 / 96卷 / 05期

基金：

美国国家卫生研究院;

关键词：

single nucleotide polymorphisms; cytosolic sulfotransferase; SULT; SULT2A1; sulfation; dehydroepiandrosterone; DHEA; pregnenolone; POLYCYSTIC-OVARY-SYNDROME; ADRENAL ANDROGENS; CRYSTAL-STRUCTURE; PROSTATE-CANCER; DHEA; SUBSTRATE; SULFONATION; METABOLISM; VARIANTS; PROTEINS;

D O I：

10.1139/bcb-2017-0341

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：655 / 662

页数：8

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