Solution structure of the reduced form of human peroxiredoxin-6 elucidated using zero-length chemical cross-linking and homology modelling

The Biochemical Journal
Roland F Rivera-SantiagoDavid W Speicher

Abstract

Peroxiredoxin-6 (PRDX6) is an unusual member of the peroxiredoxin family of antioxidant enzymes that has only one evolutionarily conserved cysteine. It reduces oxidized lipids and reactive oxygen species (ROS) by oxidation of the active-site cysteine (Cys(47)) to a sulfenic acid, but the mechanism for conversion back to a thiol is not completely understood. Moreover, it has phospholipase A2 (PLA2) activity in addition to its peroxidase activity. Interestingly, some biochemical data are inconsistent with a known high-resolution crystal structure of the catalytic intermediate of the protein, and biophysical data indicate that the protein undergoes conformational changes that affect enzyme activity. In order to further elucidate the solution structure of this important enzyme, we used chemical cross-linking coupled with high-resolution MS (CX-MS), with an emphasis on zero-length cross-links. Distance constraints from high confidence cross-links were used in homology modelling experiments to determine a solution structure of the reduced form of the protein. This structure was further evaluated using chemical cross-links produced by several homo-bifunctional amine-reactive cross-linking reagents, which helped to confirm the solution...Continue Reading

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Citations

Sep 24, 2015·Kidney International·Sara L SorrellFiona E Karet Frankl
May 6, 2015·Methods : a Companion to Methods in Enzymology·Roland F Rivera-SantiagoDavid W Speicher
Feb 3, 2016·Journal of Lipid Research·Aron B FisherSheldon I Feinstein
May 3, 2018·Journal of Lipid Research·Aron B Fisher
Jul 10, 2019·The Journal of Physiological Sciences : JPS·Lichao ZhangRunping Li
Jan 6, 2019·Antioxidants·Tom E ForshawCristina M Furdui
Oct 17, 2020·Scientific Reports·Rimpy Kaur ChowhanLaishram Rajendrakumar Singh

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