TY - JOUR
T1 - Location of the epoxide function determines specificity of the allelic variants of human glutathione transferase Pi toward benzo[c]chrysene diol epoxide isomers
AU - Pal, Ajai
AU - Desai, Dhimant
AU - Amin, Shantu
AU - Srivastava, Sanjay K.
AU - Hu, Xun
AU - Herzog, Christian
AU - Zimniak, Piotr
AU - Singh, Shivendra V.
N1 - Funding Information:
This investigation was supported in part by USPHS grants ES 09140 (awarded by the National Institute of Environmental Health Sciences), and CA 76348 and NCI-CB-77022-75 (awarded by the National Cancer Institute). The authors thank Monica Sharma and Aneel Gursahaney for technical assistance.
PY - 2000/12/8
Y1 - 2000/12/8
N2 - Carcinogenic activity of many polycyclic aromatic hydrocarbons (PAHs) is mainly attributed to their respective diol epoxides, which can be classified as either bay or fjord region depending upon the location of the epoxide function. The Pi class human glutathione (GSH) transferase (hGSTP1-1), which is polymorphic in humans with respect to amino acid residues in positions 104 (isoleucine or valine) and/or 113 (alanine or valine), plays an important role in the detoxification of PAH-diol epoxides. Here, we report that the location of the epoxide function determines specificity of allelic variants of hGSTP1-1 toward racemic anti-diol epoxide isomers of benzo[c]chrysene (B[c]C). The catalytic efficiency (k(cat)/K(m)) of V104,A113 (VA) and V104,V113 (VV) variants of hGSTP1-1 was approximately 2.3- and 1.7-fold higher, respectively, than that of the I104,A113 (IA) isoform toward bay region isomer (±)-anti-B[c]C-1,2-diol-3,4-epoxide. On the other hand, the IA variant was approximately 1.6- and 3.5-fold more efficient than VA and VV isoforms, respectively, in catalyzing the GSH conjugation of fjord region isomer (±)-anti-B[c]C-9,10-diol-11,12-epoxide. The results of the present study clearly indicate that the location of the epoxide function determines specificity of the allelic variants of hGSTP1-1 in the GSH conjugation of activated diol epoxide isomers of B[c]C. (C) 2000 Federation of European Biochemical Societies.
AB - Carcinogenic activity of many polycyclic aromatic hydrocarbons (PAHs) is mainly attributed to their respective diol epoxides, which can be classified as either bay or fjord region depending upon the location of the epoxide function. The Pi class human glutathione (GSH) transferase (hGSTP1-1), which is polymorphic in humans with respect to amino acid residues in positions 104 (isoleucine or valine) and/or 113 (alanine or valine), plays an important role in the detoxification of PAH-diol epoxides. Here, we report that the location of the epoxide function determines specificity of allelic variants of hGSTP1-1 toward racemic anti-diol epoxide isomers of benzo[c]chrysene (B[c]C). The catalytic efficiency (k(cat)/K(m)) of V104,A113 (VA) and V104,V113 (VV) variants of hGSTP1-1 was approximately 2.3- and 1.7-fold higher, respectively, than that of the I104,A113 (IA) isoform toward bay region isomer (±)-anti-B[c]C-1,2-diol-3,4-epoxide. On the other hand, the IA variant was approximately 1.6- and 3.5-fold more efficient than VA and VV isoforms, respectively, in catalyzing the GSH conjugation of fjord region isomer (±)-anti-B[c]C-9,10-diol-11,12-epoxide. The results of the present study clearly indicate that the location of the epoxide function determines specificity of the allelic variants of hGSTP1-1 in the GSH conjugation of activated diol epoxide isomers of B[c]C. (C) 2000 Federation of European Biochemical Societies.
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U2 - 10.1016/S0014-5793(00)02254-7
DO - 10.1016/S0014-5793(00)02254-7
M3 - Article
C2 - 11113459
AN - SCOPUS:0034624247
SN - 0014-5793
VL - 486
SP - 163
EP - 166
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -