Disease relevance of Gstm1

• Reduction of Gstm1 expression in the stroke-prone spontaneously hypertension rat contributes to increased oxidative stress [1].
• In the first, involving a U.S. population sample, smokers with and without lung cancer were phenotyped, and a highly significant correlation between the absence of GSTM1-1 activity and adenocarcinoma of the lung was observed.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
• The isoenzyme 3-3 of rat liver glutathione S-transferase (GST 3-3) isolated from a baculovirus expression system has been crystallized with and without inhibitor [3].

High impact information on Gstm1

• The expression of all other major forms of rat hepatic GST subunit protein, including GST Yb1, Yb2, Yb3, Yp, and Yl, was unaffected by tamoxifen treatment [4].
• The null phenotype therefore was conspicuous in liver, where GSTM1-1 ordinarily was the predominant Mu transcript, but brain and testis contained all four forms [5].
• Identification of glutathione S-transferase Yb1 mRNA as the androgen-repressed mRNA by cDNA cloning and sequence analysis [6].
• The cDNA for one of the androgen-repressed mRNAs has been identified by nucleotide sequence analysis as coding for the glutathione S-transferase Yb1 subunit [6].
• The complete amino acid sequence of the Yb2 subunit has been determined from a combination of DNA sequence analysis of pGTA/C48 and conventional protein sequence analysis of the glutathione S-transferase Yb1 Yb2 heterodimer [7].

Biological context of Gstm1

• The human homologs of Gstm1 map to chromosome 1, and belong to a group of 9 genes that show conserved synteny on rat chromosome 2 [8].
• Secretion of glutathione S-transferase isoforms in the seminiferous tubular fluid, tissue distribution and sex steroid binding by rat GSTM1 [9].
• Functionally, STF-GSTM1 appeared to serve as a steroid-binding protein by its ability to bind to testosterone and oestradiol, two important hormones in the ST that are essential for spermatogenesis, with binding constants of <9.8x10(-7) M for testosterone and 9x10(-6) M for oestradiol respectively [9].
• DNA sequencing identified one coding single nucleotide polymorphism (R202H) and multiple single nucleotide polymorphisms in the promoter region. mRNA expression changes were reflected at the protein level, with significant reductions in the SHRSP glutathione S-transferase mu type 1 [1].
• GSH conjugates of phenanthrene 9(S),10(R)-oxide and 4,5-diazaphenanthrene 9(S),10(R)-oxide were docked into the active site of both GST 3-3 and GST 4-4 [10].

Anatomical context of Gstm1

• Molecular masses of rGSTM2, rGSTM3 and rGST-Alpha from liver and testis sources were similar, unlike STF-GSTM1, which was larger by 325 Da than its liver counterpart [9].
• Microinjected glutathione S-transferase Yb subunits translocate to the cell nucleus [11].
• Glutathione-S-transferase Yb subunits were recently identified in rat brain and localized to astrocytes, ependymal cells lining the ventricles, subventricular zone cells, and tanycytes [12].
• These experiments demonstrate that glutathione S-transferase Yb subunits isolated from nuclei rapidly translocate to nuclei upon reintroduction into cell cytoplasms [11].
• The kinetic study strongly suggested that GSTs determining the higher enantioselectivity towards (R)-STO in the rat liver cytosol were the class mu enzymes, especially GST 3-3, which had the highest Kcat/Km value towards (R)-STO as well as the highest (R) to (S) ratio in the enantioselectivity among the six isoenzymes examined [13].

Associations of Gstm1 with chemical compounds

• The conformational stabilities of two homodimeric class mu glutathione transferases (GSTM1-1 and GSTM2-2) were studied by urea- and guanidinium chloride-induced denaturation [14].
• From these homology modeling and docking data, the difference in stereoselectivity between GST 3-3 and GST 4-4 for the R- and S-configured carbons of the oxirane moiety could be rationalized [10].
• GST 4-4 distinguishes itself from GST 3-3 in being much more efficient and stereoselective in the nucleophilic addition of GSH to epoxides and alpha,beta-unsaturated ketones [10].
• The concentrations of caffeic acid that inhibited reversibly 50% of the activity of different GST isoenzymes towards 1-chloro-2,4-dinitrobenzene (CDNB) (I50 values) were 58 (GST 4-4), 360 (GST 3-3) and 470 microM (GST 7-7), and higher than 640 microM for GST isoenzymes of the alpha class (GST 1-1 and 2-2) [15].
• The tertiary structure of residues 1-202 is similar to that of the corresponding region in the class mu isoform of glutathione transferase from rat, GST3-3 (Ji et al. (1992), Biochemistry, 31, 10169-10184) [16].

Other interactions of Gstm1

• Changes in tertiary structure occur as two transitions; the first is protein concentration dependent, while the second is weakly dependent (GSTM1-1) or independent (GSTM2-2) [14].
• The remaining activity towards CDNB (expressed as percentage of control) after incubating 1.25 microM-GST with 100 microM-caffeic acid for 6 hr at 37 degrees C was 34 (GST 2-2), 24 (GST 1-1), 23 (GST 4-4), 10 (GST 3-3) and 5% (GST 7-7) [15].
• In addition, DAS induced the glutathione S-transferase alpha subfamily, the glutathione S-transferase mu subfamily, and epoxide hydrolase [17].
• Three other glial proteins (vimentin, S100 and GST Yb) disappeared from infarct over a similar time course [18].

Analytical, diagnostic and therapeutic context of Gstm1

• Identification of rat liver glutathione S-transferase Yb subunits by partial N-terminal sequencing after electroblotting of proteins onto a polyvinylidene difluoride membrane from an analytical isoelectric focusing gel [19].
• Results from peptide mapping and amino acid sequence analyses indicate that CDNB modifies the cysteine residues and Tyr-115 on wild-type GST 3-3, but only Tyr-115 on CallS [20].
• Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for changes in protein level affected by EGCG (1 mg/kg weight) [21].
• Computer analysis of the circular dichroism spectra revealed that rat liver GST 3-3 contained approximately 49% alpha-helix and 24% random coil [22].
• The spatial localization of a glutathione S-transferase (rGSTM1, previously known as GST 3-3) within this model was investigated using immunohistochemistry [23].

References