Crystal structure of sulfonic peroxiredoxin Ahp1 in complex with thioredoxin Trx2 mimics a conformational intermediate during the catalytic cycle

Peroxiredoxin (Prx) is a thiol-based peroxidase that eliminates reactive oxygen species to avoid oxidative damage. Alkyl hydroperoxide reductase Ahp1 is a novel and specific typical 2-cysteine Prx. Here, we present the crystal structure of sulfonic Ahp1 complexed with thioredoxin Trx2 at 2.12 angstrom resolution. This structure implies that the transient Ahp1-Trx2 complex during the catalytic cycle already have an ability to decompose the peroxides. Structural analysis reveals that the segment glutamine23-lysine32 juxtaposed to the resolving cysteine (C-R) of Ahpl moves inward to generate a compact structure upon peroxidatic cysteine (C-P) overoxidation, resulting in the breakdown of several conserved hydrogen bonds formed by Ahp1-Trx2 complex interaction. Structural comparisons suggest that the structure of sulfonic Ahp1 represents a novel conformation of Ahp1, which can mimic a conformational intermediate between the reduced and oxidized forms. Therefore, this study may provide a new structural insight into the intermediate state in which the segment glutamine23-lysine32 juxtaposed to the cysteine31 (C-R) undergoes a conformational change upon cysteine62 (C-P) oxidation to prepare for the formation of an intermolecular C-P-C-R disulfide bond during Ahp1 catalytic cycle. (C) 2020 Elsevier B.V. All rights reserved.