Figure 1
Summary of reaction mechanisms for (A): CAT, (B): PRX, and (C): GPX. In the first step of the reaction mechanism of all PRXs and CysGPXs, and GPX7, H2O2 reacts with the peroxidatic cysteine (CP) to form a sulfenic acid (SOH) intermediate. Whilst in SecGPXs, a catalytic selenocysteine first reacts to form a selenic acid (SeOH). If a second, resolving cysteine (CR) is present (i.e., in AhpC-PRX1, PRX5 & CysGPX), this quickly reacts with the SOH to form either an inter- or intramolecular disulfide bond that is then most commonly reduced by thioredoxin (TRX), reactivating the enzyme. PRX6 instead forms a disulfide with another molecule, commonly GST, and is then recycled by glutathione (GSH), generating oxidised glutathione (GSSG). In SecGPXs the SeOH is similarly reduced by two GSH generating GSSG, whilst GPX7 is described to be reactivated via the ER protein disulfide isomerase (PDI). For PRXs under high concentrations of H2O2, SOH reacts with another molecule of H2O2 to form a sulfenic acid (SO2H), resulting in hyperoxidation. Enzymes within the subfamily, AhpC-PRX1 only may then be slowly re-activated via the enzyme sulfiredoxin (SRX) via the inactivation loop. (D): Generalised domain structure for CAT, PRX, and GPX enzyme families. CAT enzymes comprise a catalase domain and catalase-related immune -responsive (catalase_rel). Stars denote presence of active site, His and Asn respectively. All PRX enzymes comprise the domain, Alkyl hydroperoxide reductase-Thiol specific antioxidant (AphC-TSA). The subfamilies AhpC-PRX1 and PRX6 additionally commonly encode the Peroxiredoxin, C-terminal domain (1-cysPrx_C). CP (red) and CR (blue) conserved active site are displayed, residues in bold denote absolutely conserved, and underlined residues denotes amino acids that deviated from that displayed within more than one metazoan sequence. GPX enzymes comprise a single GSHPx domain. GPX enzymes may encode either CP or a catalytic Sec (S) within the active site.
