TY - JOUR
T1 - Primary and secondary structural analyses of glutathione S-transferase π from human placenta
AU - Ahmad, Hassan
AU - Wilson, Douglas E.
AU - Fritz, Richard R.
AU - Singh, Shivendra V.
AU - Medh, Rheem D.
AU - Nagle, Gregg T.
AU - Awasthi, Yogesh C.
AU - Kurosky, Alexander
N1 - Funding Information:
i This investigation was supported in part by USPHS Grants CA 27967, GM 32304, EY 04396, and CA 17701. NIH support for BIONET was to IntelliGenetics, Inc. Grant 5 U41 RR 01685. ‘Present address: Department of Oncology, School of Medicine, University of Miami, Miami, FL 33136.
PY - 1990/5/1
Y1 - 1990/5/1
N2 - The primary structure of glutathione S-transferase (GST) π from a single human placenta was determined. The structure was established by chemical characterization of tryptic and cyanogen bromide peptides as well as automated sequence analysis of the intact enzyme. The structural analysis indicated that the protein is comprised of 209 amino acid residues and gave no evidence of post-translational modifications. The amino acid sequence differed from that of the deduced amino acid sequence determined by nucleotide sequence analysis of a cDNA clone (Kano, T., Sakai, M., and Muramatsu, M., 1987, Cancer Res.47, 5626-5630) at position 104 which contained both valine and isoleucine whereas the deduced sequence from nucleotide sequence analysis identified only isoleucine at this position. These results demonstrated that in the one individual placenta studied at least two GST π genes are coexpressed, probably as a result of allelomorphism. Computer assisted consensus sequence evaluation identified a hydrophobic region in GST π (residues 155-181) that was predicted to be either a buried transmembrane helical region or a signal sequence region. The significance of this hydrophobic region was interpreted in relation to the mode of action of the enzyme especially in regard to the potential involvement of a histidine in the active site mechanism. A comparison of the chemical similarity of five known human GST complete enzyme structures, one of π, one of μ, two of α, and one microsomal, gave evidence that all five enzymes have evolved by a divergent evolutionary process after gene duplication, with the microsomal enzyme representing the most divergent form.
AB - The primary structure of glutathione S-transferase (GST) π from a single human placenta was determined. The structure was established by chemical characterization of tryptic and cyanogen bromide peptides as well as automated sequence analysis of the intact enzyme. The structural analysis indicated that the protein is comprised of 209 amino acid residues and gave no evidence of post-translational modifications. The amino acid sequence differed from that of the deduced amino acid sequence determined by nucleotide sequence analysis of a cDNA clone (Kano, T., Sakai, M., and Muramatsu, M., 1987, Cancer Res.47, 5626-5630) at position 104 which contained both valine and isoleucine whereas the deduced sequence from nucleotide sequence analysis identified only isoleucine at this position. These results demonstrated that in the one individual placenta studied at least two GST π genes are coexpressed, probably as a result of allelomorphism. Computer assisted consensus sequence evaluation identified a hydrophobic region in GST π (residues 155-181) that was predicted to be either a buried transmembrane helical region or a signal sequence region. The significance of this hydrophobic region was interpreted in relation to the mode of action of the enzyme especially in regard to the potential involvement of a histidine in the active site mechanism. A comparison of the chemical similarity of five known human GST complete enzyme structures, one of π, one of μ, two of α, and one microsomal, gave evidence that all five enzymes have evolved by a divergent evolutionary process after gene duplication, with the microsomal enzyme representing the most divergent form.
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U2 - 10.1016/0003-9861(90)90277-6
DO - 10.1016/0003-9861(90)90277-6
M3 - Article
C2 - 2327795
AN - SCOPUS:0025255437
SN - 0003-9861
VL - 278
SP - 398
EP - 408
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -