Naturally occurring Phe151Leu substitution near a conserved folding module lowers stability of glutathione transferase P1-1.
Naturally occurring Phe151Leu substitution near a conserved folding module lowers stability of glutathione transferase P1-1.
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保守折叠模块附近天然发生的 Phe151Leu 取代会降低谷胱甘肽转移酶 P1-1 的稳定性。
DOI：
10.1016/s1570-9639(03)00149-3
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Mannervik,Bengt
中科院分区：
文献类型：
--
作者：
Lin,HenryJ;Johansson,AnnSofie;Stenberg,Gun;Materi,AliciaM;Park,JaeMan;Dai,Aihua;Zhou,Haiyan;Gim,JasonSY;Kau,IrvingH;Hardy,StevenI;Parker,MichaelW;Mannervik,Bengt
Glutathione transferases (GSTs) are a family of enzymes that detoxify electrophilic compounds, such as carcinogens or drugs, by conjugating them to glutathione. The enzymes have contributed to the understanding of protein structure, due to large differences in amino acid sequence within the family, yet similar architecture and folding. Our objective was to conduct a systematic survey of GSTP1 polymorphisms and their function. Nearly all variants detected were known polymorphisms: IVS4+13C>A; Ile105Val; Ala114Val; and g.2596T>C (Ser185Ser). However, we also found a novel Phe151Leu substitution in an African-American subject (1 out of 111). Kinetic parameters for the conjugation reaction with 1-chloro-2,4-dinitrobenzene (CDNB) were determined for the novel variant enzyme purified via heterologous expression in Escherichia coli. Five substrates were used for measurement of specific activities, including isothiocyanate compounds that occur in cruciferous vegetables (benzylisothiocyanate, phenethylisothiocyanate, and sulforaphane). Such isothiocyanate substrates are potential cancer chemopreventive agents that are conjugated by GSTs. No major change in kinetic parameters was observed. However, the half-life at 50 °C of the Leu 151 enzyme was reduced to 12 min, as compared to 28 min for the Phe 151 enzyme. Residue 151 is located at the N-terminus of helix α6 in GST motif II, surrounded by hydrophobic residues, and near the conserved “hydrophobic staple” and N-capping box motifs. These local structural elements aid in formation of helix α6 and promote proper folding and protein stability. Analysis of the three-dimensional structure showed that substitution of Phe 151 with Leu produces a hydrophobic cavity in the GSTP1 core, thereby destabilizing its structure. Phe151Leu represents one of the first-described allelic variations in a protein folding motif.
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影响因子：
5.6
作者：
Johansson, AS;Stenberg, G;Mannervik, B
通讯作者：
Mannervik, B
人谷胱甘肽转移酶 P1-1 不耐热突变体的结构。
影响因子：
5.6
作者：
J. Rossjohn;W. McKinstry;A. Oakley;M. Parker;G. Stenberg;B. Mannervik;B. Dragani;R. Cocco;A. Aceto
通讯作者：
A. Aceto
DOI：
--
发表时间：
2001
期刊：
影响因子：
--
作者：
A. Johansson;B. Mannervik;O. P. E. G. Pacifici
通讯作者：
O. P. E. G. Pacifici
编码大鼠胎盘谷胱甘肽 S-转移酶 cDNA 的克隆：肝细胞癌中 mRNA 的过量产生。
DOI：
--
发表时间：
1986
期刊：
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
影响因子：
--
作者：
Knoll,BJ;Longley,M;Sell,S
通讯作者：
Sell,S
DOI：
10.1093/jnci/94.12.936
发表时间：
2002-06
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
J. Stoehlmacher;D. Park;Wu Zhang;S. Groshen;D. Tsao-Wei;Mimi C. Yu;H. Lenz
通讯作者：
J. Stoehlmacher;D. Park;Wu Zhang;S. Groshen;D. Tsao-Wei;Mimi C. Yu;H. Lenz