Catalytic site cysteines of thiol enzyme: sulfurtransferases

Abstract

Thiol enzymes have single- or double-catalytic site cysteine residues and are redox active. Oxidoreductases and isomerases contain double-catalytic site cysteine residues, which are oxidized to a disulfide via a sulfenyl intermediate and reduced to a thiol or a thiolate. The redox changes of these enzymes are involved in their catalytic processes. On the other hand, transferases, and also some phosphatases and hydrolases, have a single-catalytic site cysteine residue. The cysteines are redox active, but their sulfenyl forms, which are inactive, are not well explained biologically. In particular, oxidized forms of sulfurtransferases, such as mercaptopyruvate sulfurtransferase and thiosulfate sulfurtransferase, are not reduced by reduced glutathione but by reduced thioredoxin. This paper focuses on why the catalytic site cysteine of sulfurtransferase is redox active.

Figure 1

Comparison of the amino acid sequences around a catalytic site cysteine residue between MST and TST Sequence identity was analyzed using GENETYX (GENETYX CORPORATION). Box, a catalytic site. E, E. coli (D10496 for MST, NP_417883 for TST); H, Homo sapiens (BC009450 for MST, D87292 for TST); L. Leishmania (CAC85741); P1 and P2, Arabidopsis thaliana (AB032864 and AB032865 for MSTs); R, Rattus norvegicus (D50564 for MST, BC088449 for TST). Underlined amino acids, consensus sequences for MST or TST.

Figure 2

Model for the two α-helix dipoles of TST and MST, each structure is represented using RasMol. (a) bovine liver TST from 1DP2, red ribbon structure represents two helix-dipoles (α9 and α10) and ball-and-stick model in yellow represents a catalytic site Cys247. (b) Leishmania major MST from 1CKG red ribbon structure represents two helix-dipoles (α8 and α9), red ribbon structure represents two helix-dipoles (α8 and α9), and ball-and-stick model in yellow represents a catalytic site Cys253.

Figure 3

Thioredoxin oxidase activity of TST and thioredoxin peroxidase activity of MST, Proposed thioredoxin oxidase activity of TST (a) reported by Nandi and colleagues [63], which is same as thioredoxin peroxidase activity of MST (b) (from Figure  10 of Nagahara et al. Current Medical Chemistry 2009. 16: 4422). Trx: thioredoxin; TRD: thioredoxin reductase.