Description

The peroxiredoxins are included in haem-free thiol peroxidase family as well as glutathione peroxidases (GPx). Both families, although totally different from their primary sequence, have in common the formation of a sulfenic acid on the N-terminal catalytic cysteine during the first step of peroxide reduction.
The peroxiredoxin family is characterized by the presence of a highly conserved cysteine residue called peroxidatic cysteine, surrounded by various conserved amino acids differing with the Prx group considered (1-Cys Prx: T[P/S][V/I]]C[T/S]TE, typical 2-Cys : F[T/S]FVCP[T/S]E, atypical 2-CysPrx from plants: CTK[Q/E]AC or atypical 2-Cys fusion: LPGAxTPTCS).

Most typical and atypical 2-Cys Prx form an intra- or intermolecular disulfide bridge between the peroxidatic and a resolving cysteine which is then reduced by thioredoxin.
Nevertheless, some Prx II and PrxGrx, belonging to the atypical 2-Cys Prx, are reduced respectively by GSH together or not with Grx.

For 1-Cys Prx, the physiological reductant is still a mater of debate but GSH, cyclophilin, glutathione-S-transferase or ascorbate have been proposed to act as reductants. The peroxiredoxin encoding sequences is detected in all kingdoms. Exceptions can be observed for the certain classes: atypical 2-Cysteine peroxiredoxin PrxQ/BCP are absent from animals and PrxII-glutoredoxin fusion proteins are only detected in prokaryotes. Peroxiredoxin sequences are classified into one of six distinct subclasses as largely described in peroxiredoxin database PREX

1CysPrx subfamily (Prx6): Peroxiredoxins containing only one conserved cysteine, which serves as the peroxidatic cysteine.
They are homodimeric thiol-specific antioxidant (TSA) proteins that confer a protective role in cells by reducing and detoxifying hydrogen peroxide, peroxynitrite, and organic hydroperoxides. Having no resolving cysteine, the oxidized enzyme is resolved by an external small-molecule or protein reductant such as thioredoxin or glutaredoxin. Similar to typical 2CysPrx, 1CysPrx forms a functional dimeric unit with a B-type interface, as well as a decameric structure which is stabilized in the reduced form of the enzyme. Other oligomeric forms, tetramers and hexamers, have also been reported. Mammalian 1CysPrx are cytosol and is expressed at high levels in brain, eye, testes and lung. The seed-specific plant 1CysPrx protect tissues from reactive oxygen species during desiccation and are also called rehydrins.

AhpC-Prx1 Typical 2CysPrx subfamily (AhpC-Prx1): 2CysPrxs are thiol-specific antioxidant (TSA) proteins, which confer a protective role in cells through its peroxidase activity by reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides. The functional unit 2CysPrx is a homodimer. A unique intermolecular redox-active disulfide center is utilized for its activity. Upon reaction with peroxides, its peroxidatic cysteine is oxidized into a sulfenic acid intermediate which is resolved by bonding with the resolving cysteine from the other subunit of the homodimer.
This intermolecular disulfide bond is then reduced by thioredoxin, tryparedoxin or AhpF. 2CysPrx, like 1CysPrx, form decamers which are stabilized by reduction of the active site cysteine. 2CysPrx interacts through beta strands at one edge of the monomer (B-type interface) to form the functional homodimer, and uses an A-type interface (similar to the dimeric interface in atypical 2-cys PRX and PrxV) at the opposite end of the monomer to form the stable decameric (pentamer of dimers)

Atypical 2-Cysteine peroxiredoxin type V and type II, PRX5-like subfamily (Prx5) : HsPrxV is a homodimeric peroxidase, constitutively expressed and found in mitochondria, peroxisomes and cytosol. HsPrxV could have an important antioxidant role in this organelles (sources of ROS), as well as a role in the control of signal transduction. HsPrxV has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. HsPrxV is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX.

Atypical 2-cys peroxiredoxin subfamily, TRX-dependent thiol peroxidase (TPx): TPx is a bacterial periplasmic peroxidase which differs from other peroxiredoxins in that it shows substrate specificity toward alkyl hydroperoxides over hydrogen peroxide. TPx is able to resolve this intermediate by forming an intramolecular disulfide bond with a conserved C-terminal cysteine (the resolving cysteine), which can then be reduced by thioredoxin.

Atypical 2-cys peroxiredoxin type Q subfamily and Bacterioferritin comigratory protein (BCP) subfamily (BCP-PrxQ): widely expressed in pathogenic bacteria, that protect cells against toxicity from reactive oxygen species by reducing and detoxifying hydroperoxides. The protein was named BCP based on its electrophoretic mobility before its function was known. BCP shows substrate selectivity toward fatty acid hydroperoxides rather than hydrogen peroxide or alkyl hydroperoxides. BCP contains the peroxidatic cysteine but appears not to possess a resolving cysteine (some sequences, not all, contain a second cysteine but its role is still unknown). Unlike other Peroxiredoxins, BCP exists as a monomer. The plant homolog of BCP is PrxQ, which is expressed only in leaves and is cellularly localized in the chloroplasts and the guard cells of stomata.

AhpE-like subfamily (AhpE): composed of proteins similar to Mycobacterium tuberculosis AhpE. MtAhpE is described as a 1CysPrx because of the absence of a resolving cysteine. The structure and sequence of AhpE, however, show greater similarity to 2CysPrxs than 1CysPrxs. The absence of a resolving cysteine suggests that functional MtAhpE is regenerated by an external reductant. AhpE forms dimers and octamers.