Structural highlights
Function
[PRDX4_HUMAN] Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.[1]
Publication Abstract from PubMed
Prx4 (peroxiredoxin 4) is the only peroxiredoxin located in the ER (endoplasmic reticulum) and a proposed scavenger for H2O2. In this work we presented crystal structures of human Prx4 in three different redox forms and characterized the reaction features of Prx4 with H2O2. Prx4 exhibits a toroid-shaped decamer constructed of five catalytic dimers. Structural analysis revealed conformational changes around helix alpha2 and the C-terminal reigon with a YF motif from the partner subunit, which are required for inter-chain disulfide formation between Cys87 and Cys208, a critical step of the catalysis. The structural explanation for the restricting role of the YF motif on the active site dynamics is provided in detail. Prx4 has a high reactivity to H2O2, but is susceptible to over-oxidation and consequent inactivation by H2O2. Either deletion of the YF motif or dissociation into dimers decreased the susceptibility of Prx4 to over-oxidation by increasing the flexibility of Cys87.
Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4.,Wang X, Wang L, Wang X, Sun F, Wang CC Biochem J. 2011 Sep 15. PMID:21916849[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jin DY, Chae HZ, Rhee SG, Jeang KT. Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem. 1997 Dec 5;272(49):30952-61. PMID:9388242
- ↑ Wang X, Wang L, Wang X, Sun F, Wang CC. Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4. Biochem J. 2011 Sep 15. PMID:21916849 doi:10.1042/BJ20110380
