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

Fu-Ming Lian; Yong-Liang Jiang; Wancai Yang; Xiangwei Yang

doi:10.1016/j.ijbiomac.2020.06.065

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

Int J Biol Macromol. 2020 Oct 15:161:1055-1060. doi: 10.1016/j.ijbiomac.2020.06.065. Epub 2020 Jun 9.

Authors

Fu-Ming Lian¹, Yong-Liang Jiang², Wancai Yang³, Xiangwei Yang⁴

Affiliations

¹ Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, Shandong 272067, People's Republic of China; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China. Electronic address: fmlian@mail.jnmc.edu.cn.
² Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
³ Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, Shandong 272067, People's Republic of China; Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
⁴ Institute of Behavioral Medicine Education of Shandong Province, Jining Medical University, Jining, Shandong 272067, People's Republic of China; Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, Shandong 272067, People's Republic of China. Electronic address: lana826@mail.ustc.edu.cn.

PMID: 32531362
DOI: 10.1016/j.ijbiomac.2020.06.065

Abstract

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.

Keywords: Alkyl hydroperoxide reductase; Catalytic cycle; Complex structure; Conformational change; Peroxiredoxin; X-ray crystallography.

MeSH terms

Binding Sites
Catalysis
Cloning, Molecular
Crystallography, X-Ray
Models, Biological
Models, Molecular*
Oxidation-Reduction
Peroxiredoxins / chemistry*
Peroxiredoxins / metabolism
Protein Binding
Protein Conformation*
Structure-Activity Relationship
Thioredoxin h / chemistry*
Thioredoxin h / metabolism

Substances

Thioredoxin h
Peroxiredoxins