5ZPV

Solution Structure of Thioredoxin-Like Effector Protein (TRX3) from Edwardsiella piscicida

5ZPV の概要

• エントリーDOI: 10.2210/pdb5zpv/pdb
• NMR情報: BMRB: 36180
• 分子名称: Thioredoxin (H-type,TRX-H) (1 entity in total)
• 機能のキーワード: inhibitor, redox activity, reactivity, active site, thiol-disulfide oxidoreductase, oxidoreductase
• 由来する生物種: Edwardsiella tarda EIB202
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13694.31

構造登録者

Sayed, A.M.,Mok, Y.K. (登録日: 2018-04-16, 公開日: 2019-05-22, 最終更新日: 2024-05-15)

主引用文献

Sayed, A.,Chakraborty, S.,Leung, K.Y.,Sugii, S.,Mok, Y.K.
Trxlp, a thioredoxin-like effector from Edwardsiella piscicida inhibits cellular redox signaling and nuclear translocation of NF-kappa B.
Int.J.Biol.Macromol., 148:89-101, 2020

PubMed Abstract: Redox signaling and homeostasis are essential for cell survival and the immune response. Peroxiredoxin (Prx) modulates the level of HO as a redox signal through HO decomposition. The redox activity of thioredoxin (Trx) is required as a reducing equivalent to regenerate Prx. Edwardsiella piscicida is an opportunistic Gram-negative enteric pathogen that secretes a novel Trx-like effector protein, ETAE_2186 (Trxlp). Trxlp has unique structural properties compared with other Trx proteins. In enzymatic and binding assays, we confirmed Trxlp to be redox-inactive due to the low reactivity and flexibility of the resolving cysteine residue, C35, at the active site motif "WCXXC". We identified key residues near the active site that are critical for reactivity and flexibility of C35 by site-directed mutagenesis analysis. NMR titration experiment demonstrated prolong inhibitory interaction of Trxlp with Prx1 resulting in the repression of Prx1-mediated HO decomposition leading to increased ROS accumulation in infected host cells. Increased ROS in turn prevented nuclear translocation of NF-κB and inhibition of NF-κB target genes, leading to bacterial survival and enhanced replication inside host cells. Targeting Trxlp-mediated virulence promises to attenuate E. piscicida infection.

PubMed: 31945434
DOI: 10.1016/j.ijbiomac.2020.01.114

実験手法

SOLUTION NMR