AhpF and other NADH:peroxiredoxin oxidoreductases, homologues of low M_r thioredoxin reductase

Abstract

A group of bacterial flavoproteins related to thioredoxin reductase contain an additional < 200-amino-acid domain including a redox-active disulfide center at their N-termini. These flavoproteins, designated NADH:peroxiredoxin oxidoreductases, catalyze the pyridine-nucleotide-dependent reduction of cysteine-based peroxidases (e.g. Salmonella typhimurium AhpC, a member of the peroxiredoxin family) which in turn reduce H 2 O 2 or organic hydroperoxides. These enzymes catalyze rapid electron transfer (k cat . 165 s 21 ) through one tightly bound FAD and two redox-active disulfide centers, with the N-terminal-most disulfide center acting as a redox mediator between the thioredoxin-reductase-like part of these proteins and the peroxiredoxin substrates. A chimeric protein with the first 207 amino acids of S. typhimurium AhpF attached to the N-terminus of Escherichia coli thioredoxin reductase exhibits very high NADPH:peroxiredoxin oxidoreductase and thioredoxin reductase activities. Catalytic turnover by NADH:peroxiredoxin oxidoreductases may involve major domain rotations, analogous to those proposed for bacterial thioredoxin reductase, and cycling of these enzymes between two electron-reduced (EH 2 ) and four electron-reduced (EH 4 ) redox states.

Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation

“…TR, TRX, and NADPH comprise a highly conserved, ubiquitous system (Mustacich and Powis, 2000) that plays an important role in the redox regulation of multiple intracellular processes, including DNA synthesis, cell growth, and resistance to cytotoxic agents that induce oxidative stress and apoptosis Williams et al, 2000;Oberley et al, 2001). TR is a homodimeric selenocysteine-containing protein that catalyses the NADPH-dependent reduction of TRX as well as numerous other oxidized cellular proteins Poole et al, 2000). There are two confirmed forms of mammalian TRs, TR1 and TR2, both of which share in common a conserved -Cys-ValAsn-Val-Gly-Cys-redox catalytic motif thought to play a central role in the redox function of TR (Mustacich and Powis, 2000;Powis et al, 1998).…”

Defence of Rhizobium etli bacteroids against oxidative stress involves a complexly regulated atypical 2‐Cys peroxiredoxin

“…Compared with thioredoxin, DTT was approximately 10 times more potent as an electron donor for PrxS. This could mean that the in vivo reduction of PrxS occurs through another (dedicated) thiol-dependent oxidoreductase, like for instance the bacterial AhpF homologues known as NADH:peroxiredoxin oxidoreductases (Poole et al, 2000). On the other hand, database searches revealed that both the glutaredoxin and thioredoxin pathways are present in rhizobia (http://www.kazusa.or.jp/rhizobase/).…”

Vibrio cholerae Thiol Peroxidase-Glutaredoxin Fusion Is a 2-Cys TSA/AhpC Subfamily Acting as a Lipid Hydroperoxide Reductase

“…AhpC and BCP are all bacterial members of the ubiquitous thiol peroxidase (TPx) (TSA/AhpC) family (7)(8)(9)(10)(11). For AhpC, reduction of peroxide is achieved by a specialized electron donor, AhpF (12), whereas BCP and p20 receive electrons from a reducing system composed of Trx and Trx reductase (11,13). P20 has been characterized as a periplasmic protein (9) that has been reported to exist in Gram-negative bacteria such as Escherichia coli (9), whereas AhpC and BCP as cytoplasmic proteins have been found in all species of bacteria (14).…”