Mutant AhpC peroxiredoxins suppress thiol-disulfide redox deficiencies and acquire deglutathionylating activity.

Molecular Cell
Yuji YamamotoL B Poole

Abstract

The bacterial peroxiredoxin AhpC, a cysteine-dependent peroxidase, can be converted through a single amino acid insertion to a disulfide reductase, AhpC*, active in the glutathione and glutaredoxin pathway. Here we show that, whereas AhpC* is inactive as a peroxidase, other point mutants in AhpC can confer the in vivo disulfide reductase activity without abrogating peroxidase activity. Moreover, AhpC* and several point mutants tested in vitro exhibit an enhanced reductase activity toward mixed disulfides between glutathione and glutaredoxin (Grx-S-SG), consistent with the in vivo requirements for these components. Remarkably, this Grx-S-SG reductase activity relies not on the peroxidatic cysteine but rather on the resolving cysteine that plays only a secondary role in the peroxidase mechanism. Furthermore, putative conformational changes, which impart this unusual Grx-S-SG reductase activity, are transmissible across subunits. Thus, AhpC and potentially other peroxiredoxins in this widespread family can elaborate a new reductase function that alleviates disulfide stress.

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Citations

Mar 12, 2011·Chemical Research in Toxicology·Gerardo Ferrer-SuetaAna Denicola
May 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Melinda J FaulknerJon Beckwith
Apr 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Morgan Anne FeeneyJonathan Beckwith
Jan 9, 2009·The Journal of Biological Chemistry·Jon Beckwith
Aug 31, 2010·Antioxidants & Redox Signaling·Chananat KlomsiriLeslie B Poole
Oct 26, 2010·Antioxidants & Redox Signaling·Andrea HallP Andrew Karplus
Oct 9, 2012·Journal of Bacteriology·Li Ma, Shelley M Payne
Oct 1, 2009·Microbial Cell Factories·Georgios SkretasGeorge Georgiou
Jun 5, 2013·Current Opinion in Structural Biology·Rene AssenbergLorenz M Mayr
May 30, 2009·The FEBS Journal·Andrea HallLeslie B Poole
May 14, 2011·Biotechnology Journal·Gustavo SalinasCecilia Fernández
Nov 17, 2011·Protein Expression and Purification·Mehmet Berkmen
May 7, 2016·Free Radical Biology & Medicine·Ché S PillayJohann M Rohwer
Aug 12, 2021·Redox Report : Communications in Free Radical Research·Ché S Pillay, Nolyn John

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