Thioredoxin-dependent Redox-sensing Molecular Switches in Hydrogen Sulfide and/or Polysulfides Producing Enzyme, 3-Mercaptopyruvate Sulfurtransferase

The rat 3-mercaptopyruvate sulfurtransferase (MST), a multifunctional enzyme, has redox-sensing molecular switches, a catalytic Cys247 and two cysteines, Cys154 and Cys263, on the outer surface of the enzyme. These switches are reduced or oxidized according to the redox state of their surrounding environment and require a redox active cysteine in thioredoxin (Trx) to interact with MST. Recently, MST has been demonstrated to be involved in the production of possible signaling molecules such as hydrogen sulfide, polysulfides, and/or sulfur oxides. However, the relationship between the production of signaling molecule(s) and action of these redox-sensing molecular switches has not been clarified, and a precise investigation of this relationship is underway. Received: November 07, 2015; Accepted: December 15, 2015; Published: December 18, 2015 state via redox-sensing molecular switches, which are exposed cysteines. Rat MST (RnMST) has five cysteines, Cys64, Cys154, Cys247, Cys254, and Cys263. Cys64 and Cys254 are buried cysteines, while the other cysteines are exposed [14]. Cys247 is a catalytic cysteine, and Cys154 and Cys263 are positioned at the surface of the enzyme; these cysteines function as redox-sensing molecular switches. Cys154 is a unique residue in RnMST. Furthermore, thioredoxins (Trxs) have redox-active cysteines. Escherichia coli Trx (EcTrx) has two redox active cysteines, one of which interacts with RnMST [15]. Properties of intermolecular switches of RnMST Cys154 and Cys263, which are positioned the surface of RnMST, form dimers via disulfide bonds [15]. Activities of wild-type and C64S (Cys64 is replaced with Ser) and C254S mutant RnMSTs were significantly increased after treatment with reduced EcTrx or EcTrx with a reducing system (Escherichia coli Trx reductase and NADPH) [15]. However, activities of C154S, C263S, and C154S/ C263S (Cys64 and Cys64 are replaced with Ser) mutant RnMSTs were not significantly increased by reduction [15]. These findings suggest that Cys154 and Cys263 are Trx-dependent redox-sensing molecular switches for regulation of MST activity, probably via the induction of conformational changes [15].