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 Å 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 Ahp1 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. • 2.12 Å resolution crystal structure of sulfonic Ahp1 in complex with Trx2 is provided. • Transient Ahp1-Trx2 complex already possess an ability to decompose the peroxides. • Segment Gln23–Lys32 of Ahp1 moves inward upon peroxidatic cysteine overoxidation. • Conserved hydrogen bonds breakdown of Ahp1-Trx2 caused by movement of Gln23–Lys32. • Provided structure can mimic an Ahp1 intermediate between reduced and oxidized forms. [ABSTRACT FROM AUTHOR]