5ZPV

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

Summary for 5ZPV

• Entry DOI: 10.2210/pdb5zpv/pdb
• NMR Information: BMRB: 36180
• Descriptor: Thioredoxin (H-type,TRX-H) (1 entity in total)
• Functional Keywords: inhibitor, redox activity, reactivity, active site, thiol-disulfide oxidoreductase, oxidoreductase
• Biological source: Edwardsiella tarda EIB202
• Total number of polymer chains: 1
• Total formula weight: 13694.31

Authors

Sayed, A.M.,Mok, Y.K. (deposition date: 2018-04-16, release date: 2019-05-22, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

SOLUTION NMR