Thioltransferase activity of bovine lens glutathione S-transferase

Abstract

A Mu-class glutathione S-transferase purified to electrophoretic homogeneity from bovine lens displayed thioltransferase activity, catalysing the transthiolation reaction between GSH and hydroxyethyldisulphide. The thiol-transfer reaction is composed of two steps, the formation of GSSG occurring through the generation of an intermediate mixed disulphide between GSH and the target disulphide. Unlike glutaredoxin, which is only able to catalyse the second step of the transthiolation process, glutathioneS-transferase catalyses both steps of the reaction. Data are presented showing that bovine lens glutathione S-transferase and rat liver glutaredoxin, which was used as a thioltransferase enzyme model, can operate in synergy to catalyse the GSH-dependent reduction of hydroxyethyldisulphide.

Identification, Characterization, and Crystal Structure of the Omega Class Glutathione Transferases

“…Similarities in the protein fold of the glutaredoxins and the N-terminal domain of the cytosolic GSTs have been noted (34), and low thiol transferase activity (74.3 nmol/mg/min) has been attributed to a Mu class GST from bovine lens (35). In other unpublished studies we examined the thiol transferase activity of a range of GSTs from the Alpha, Mu, Pi, Theta, and Zeta classes (GSTA 1-1, GST 2-2, GSTA 4-4, GSTM 1-1, GSTM 2-2, GSTM 3-3, GSTM 4-4, GSTP 1-1, GSTT 2-2, GSTT 1-1, GST Z 1-1).…”

Regulation of Cell Physiology and Pathology by Protein S-Glutathionylation: Lessons Learned from the Cardiovascular System

“…The authors noted that no S-glutathionylated protein was formed in these null mice and using isolated protein, they elegantly demonstrated that sulfenic acid formation on aldose reductase was required before GST could transfer GSH to the protein leading to the formation of a mixed disulfide (162,171). These data suggest that GST or other similar proteins can be used as a carrier of GSH and act as an intermediate in the Sglutathionylation process of target proteins (42). Furthermore, GSTs might also provide localized redox signaling.…”

Role of Glutathione S-Transferases in Lens under Oxidative Stress

“…50,51) Furthermore, GSTM exhibits a dethiolate activity such as that of thioltransferase, suggesting that GSTM plays an important role in the cleavage of the mixed disulfides produced under oxidative stress. 19,26) These results suggest that GSTs play a role as an important anti-oxidant enzyme under oxidative stress. Indeed, epidemiological studies have been presented the implication of GST M1 having an important role in cataractogenesis.…”

“…The thioltransferase-like (TTase-like) activity is the most characteristic property of GSTM. 19) The first report of this activity was presented in a paper on bovine lens GSTM by Raghavachari, N. et al 26) TTase, a small enzyme of < 10 kDa, can catalyze the thiol/ disulfide exchange reaction between small molecular weight thiols and proteins, and plays an important role in the redox regulation of protein thiols in living cells. [27][28][29][30] We have previously reported that TTase displays a strong sensitivity against oxidants, including disulfides.…”

“…Including GSH-conjugation activity, [13][14][15][16][17] GSTs are a typical multifunctional enzyme which plays a role in binding to hydrophobic compounds (ligandin), 18) as a thioltransferase-like redox regulator, 19) Se-independent GSH-peroxidase 20) and steroid isomerase. 21) The unique properties of the major class of GST are described in the following.…”