Crystal structure of Akkermansia muciniphila peroxiredoxin reveals a novel regulatory mechanism of typical 2‐Cys Prxs by a distinct loop

Abstract

Edited by Stuart FergusonPeroxiredoxins (Prxs) are thiol-specific antioxidant proteins commonly found in organisms that protect cells from the damage of reactive oxygen species produced by metabolism and that participate in cell signaling. The Prx from the bacterium Akkermansia muciniphila (AmPrx) is a typical 2-Cys Prx characterized by two conserved cysteines: Cys49 and Cys183. Here, we verified the peroxidase activity of AmPrx and determined its crystal structure in reduced form, which is a doughnut-shaped decamer composed of five dimers. Particularly, a distinct loop between the a4 helix and b6 strand is involved in the decameric interaction. Deletion of this loop destroys the decameric structure and significantly decreases the peroxidase activity of AmPrx. Our findings reveal a novel regulatory mechanism of typical 2-Cys Prx, in which the a4-b6 loop affects the assembly of Prx and, therefore, regulates its peroxidase activity.

Omega 3‐rich Camelina sativa oil in the context of a weight loss program improves glucose homeostasis, inflammation and oxidative stress in patients with NAFLD: A randomised placebo‐controlled clinical trial

“…46 It was reported that A. muciniphila alleviated OS in diabetic rats 47 due to owing thiol specific antioxidant proteins such as typical 2-Cys peroxiredoxins as a family of thioredoxin (Trx)-scaffold enzymes and ubiquitous. 48 Also, Bifidobacterium longum and Lactobacillus acidophilus inhibit lipids peroxidation by scavenging ROS, 49 reducing MDA levels and increasing SOD and TAC levels. 5 Furthermore, Clostridium perfringens, probably, triggers OS by α-toxin production, and activation of mitogen-activated protein kinase/ERK kinase/extracellularsignal-regulated kinase (MEK/ERK), protein kinase C, and NF-κB pathways.…”

“…Costantini et al reported that OM3FA intake stimulated the growth of A. muciniphila , Bifidobacteria , Lactobacilli , Faecalibacterium , Roseburia , and inhibited some pathogenic bacteria, such as the Enterobacteriaceae , Clostridium , and Streptococcus 46 . It was reported that A. muciniphila alleviated OS in diabetic rats 47 due to owing thiol specific antioxidant proteins such as typical 2‐Cys peroxiredoxins as a family of thioredoxin (Trx)‐scaffold enzymes and ubiquitous 48 . Also, Bifidobacterium longum and Lactobacillus acidophilus inhibit lipids peroxidation by scavenging ROS, 49 reducing MDA levels and increasing SOD and TAC levels 5 .…”

Camelina oil in the context of a weight loss programs improves glucose homeostasis, inflammation and oxidative stress in NAFLD patients: A randomized, triple -blind, placebo-controlled clinical trial

“…49 It was reported that A. muciniphila alleviated OS in diabetic rats 50 due to having thiol specific antioxidant proteins such as typical 2-Cys Peroxiredoxins as a family of thioredoxin (Trx)-scaffold enzymes and ubiquitous. 51 Bifidobacterium longum and Lactobacillus acidophilus inhibited lipids peroxidation by scavenging ROS 52 , reducing MDA levels and increasing SOD and TAC levels. 5 Also, Clostridium perfringens, probably, triggers OS by α-toxin production, and activation of mitogen-activated protein kinase/ERK kinase/extracellular-signal-regulated kinase (MEK/ERK), protein kinase C, and NF-κB pathways.…”