title: AhpF and other NADH:peroxiredoxin oxidoreductases, homologues of low Mr thioredoxin reductase.
abstract: A group of bacterial flavoproteins related to thioredoxin reductase contain an additional approximately 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 H2O2 or organic hydroperoxides. These enzymes catalyze rapid electron transfer (kcat > 165 s-1) 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 (EH2) and four electron-reduced (EH4) redox states.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA. lbpoole@wfubmc.edu
authors.forename: L B
authors.initials: LB
authors.lastname: Poole
authors.forename: C M
authors.initials: CM
authors.lastname: Reynolds
authors.forename: Z A
authors.initials: ZA
authors.lastname: Wood
authors.forename: P A
authors.initials: PA
authors.lastname: Karplus
authors.forename: H R
authors.initials: HR
authors.lastname: Ellis
authors.forename: M
authors.initials: M
authors.lastname: Li Calzi
mesh_terms: D000595:Amino Acid Sequence; D029968:Escherichia coli Proteins; D005420:Flavoproteins / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D008970:Molecular Weight; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D054464:Peroxiredoxins; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D005420:Flavoproteins; D010544:Peroxidases; D054464:Peroxiredoxins; C515937:ahpC protein, E coli; D009247:NADH, NADPH Oxidoreductases; C515938:ahpF protein, E coli; C416102:NADH peroxiredoxin oxidoreductase; D013880:Thioredoxin-Disulfide Reductase