Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals.
Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals.
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谷胱甘肽 s-转移酶 pi 1 的变体表现出不同的酶活性和重金属抑制作用。
DOI：
10.1016/j.tiv.2012.02.005
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发表时间：
2012-06
影响因子：
3.2
通讯作者：
Basu, Niladri
中科院分区：
文献类型：
--
作者：
Goodrich, Jaclyn M.;Basu, Niladri
在流行病学队列中，谷胱甘肽s-转移酶pi 1 （GSTP1; Ile/Val 105, Ala/Val 114）的非同义单核苷酸多态性与毒物代谢的改变有关。我们探讨了GSTP1基因型对体外酶动力学和重金属抑制的影响。4种GSTP1同工酶（105/114:Ile/Ala, Val/Ala, Ile/Val, Val/Val）在大肠杆菌中表达并纯化。测定谷胱甘肽与1-氯-2,4-二硝基苯（CDNB）偶联率的酶活性测定显示，不同基因型的动力学参数差异显著（p<0.01）。含有Ile105的酶具有更好的催化效率和对CDNB的亲和力（平均±SEM: Ile105 Ala114 Km= 0.33±0.07 mM vs Val105 Ala114 Km=1.15±0.07 mM）。在用汞（无机- HgCl2、甲基汞- MeHg）、硒、镉、铅、砷和锰处理后，评估了重金属对GSTP1活性的抑制作用。HgCl2 （IC50范围：24.1 ~ 172 μM）、MeHg （93.9 ~ 480 μM）和硒（43.7 ~ 62.8 μM）对所有同酶均有抑制作用。基因型对汞的抑制作用有显著影响，其中GSTP1 Ile105 Val114对HgCl2和MeHg的抑制作用最不敏感，Val105 Ala114最敏感。总的来说，GSTP1的两个非同义多态性的基因型影响了与亲电底物相关的酶动力学和两种汞的抑制作用。
Nonsynonymous single nucleotide polymorphisms in glutathione s-transferase pi 1 (GSTP1; Ile/Val 105, Ala/Val 114) have been associated with altered toxicant metabolism in epidemiological cohorts. We explored the impact of GSTP1 genotype on enzyme kinetics and heavy metal inhibition in vitro. Four GSTP1 allozymes (105/114: Ile/Ala, Val/Ala, Ile/Val, Val/Val) were expressed in and purified from E. coli. Enzyme activity assays quantifying the rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) revealed significant differences in kinetic parameters depending on genotype (p<0.01). Allozymes with Ile105 had better catalytic efficiency and greater affinity for CDNB (mean ±SEM: Ile105 Ala114 Km= 0.33±0.07 mM vs. Val105 Ala114 Km=1.15±0.07 mM). Inhibition of GSTP1 activity by heavy metals was assessed following treatment with mercury (inorganic- HgCl2, methylmercury- MeHg), selenium, cadmium, lead, arsenic, and manganese. All allozymes were inhibited by HgCl2 (IC50 range: 24.1–172 μM), MeHg (93.9–480 μM), and selenium (43.7–62.8 μM). Genotype significantly influenced the potency of mercury with GSTP1 Ile105 Val114 the least sensitive and Val105 Ala114 the most sensitive to inhibition by HgCl2 and MeHg. Overall, genotype of two nonsynonymous polymorphisms in GSTP1 influenced enzyme kinetics pertaining to an electrophilic substrate and inhibition by two mercury species.
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影响因子：
5.6
作者：
Johansson, AS;Stenberg, G;Mannervik, B
通讯作者：
Mannervik, B
影响因子：
3.5
作者：
Adamis, PDB;Gomes, DS;Eleutherio, ECA
通讯作者：
Eleutherio, ECA
影响因子：
3.8
作者：
Kojima, C;Qu, W;Sakurai, T
通讯作者：
Sakurai, T
DOI：
10.1016/0272-0590(85)90165-4
发表时间：
1985-01-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
BALLATORI, N;CLARKSON, TW
通讯作者：
CLARKSON, TW
DOI：
10.1097/00008571-200210000-00006
发表时间：
2002-10-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Ishimoto, TM;Ali-Osman, F
通讯作者：
Ali-Osman, F