EC Number   |
General Information  |
Reference |
|---|
   1.8.98.2 | evolution |
AtSrx has more positive charges than human enzyme HsSrx. The theoretical pI of AtSrx is 9.86, much higher than 5.47 of HsSrx. There are 10 arginine residues and 7 lysine residues in AtSrx but only 5 arginine residues and 3 lysine residues in HsSrx. For negatively charged amino acids residues, there are 6 glutamic acid residues and 4 aspartic acid residues in AtSrx, while there are 2 glutamic acid residues and 8 aspartic acid residues in HsSrx. Abundant charged amino acids of AtSrx provide more positive charge at ADP binding pocket and more interaction with active |
764076 |
| 1.8.98.2 | malfunction |
inhibition of sulfiredoxin (Srx), which participates in antioxidant mechanisms, induces ROS-mediated cancer cell death |
765246 |
| 1.8.98.2 | malfunction |
loss of the extended active site interface within engineered peroxiredoxin isozymes, Prx2 and Prx3, dimers yields variants more resistant to hyperoxidation and repair by enzyme Srx |
763914 |
| 1.8.98.2 | malfunction |
Srx knockdown sensitizes lung cancer cells to endoplasmic reticulum (ER) stress-induced cell death. Inhibition of Srx results in oxidative stress-induced mitochondrial damage and caspase activation, leading to the apoptosis of lung adenocarcinoma cells. Mutation of Cys99 to Ala (C99A) leads to a complete loss of both enzymatic activity and binding to substrates such as Prxs |
765061 |
| 1.8.98.2 | more |
Cys99 of Srx is critical for its catalytic activity |
765061 |
| 1.8.98.2 | more |
the crystal structure of sulfiredoxin from Arabidopsis thaliana (AtSrx) displays a typical ParB/Srx fold with an ATP bound at a conservative nucleotide binding motif GCHR. Both the ADP binding pocket and the putative AtSrx-AtPrxA interaction surface of AtSrx are more positively charged comparing to HsSrx, suggesting a robust mechanism of AtSrx. Complex formation analysis of enzyme AtSrx with wild-type and F149Q/C241S mutant AtPrxA substrates |
764076 |
| 1.8.98.2 | more |
the decameric Srx-Prx1 complex reveals extended binding interface, human Prx1 and Prx2 form a decameric toroid. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. Structural basis for the ability of Srx to reduce the hyperoxidized form of human Prxs, juxtaposition of the two active-site interfaces of the two proteins and wrapping of the Prx C-terminus around Srx in an essential interaction, overview |
763914 |
| 1.8.98.2 | physiological function |
2-Cys peroxiredoxins (Prxs) are highly abundant peroxidases that play as peroxide sensors promoting H2O2 signaling and oxidative stress resistance in respond to elevated oxidative levels. Prxs use a peroxidatic cysteine (Cys-SpH) to catalytically decompose peroxides. During normal catalysis, the peroxidatic Cys residue (Cys-SpH) is oxidized to Cys sulfenic acid (Cys-SpOH) and further inactivation by peroxidation of the peroxidatic cysteine residue to Cys sulfinic acid (Cys-SpO2-). Importantly, Prxs can be reactivated with the Cys-SPO2- moiety reduced to Cys sulfenic acid (Cys-SpOH) by a repaired enzyme known as sulfiredoxin (Srx). This reversible event is a physiologically important process against the oxidative stress that can allow cells to return to homeostasis |
764076 |
| 1.8.98.2 | physiological function |
enzyme induction is the pivotal compensatory protection mechanism against oxidative stress in diabetes or hyperglycaemia |
742457 |
| 1.8.98.2 | physiological function |
exposure of low steady-state levels ofH2O2 to A-549 or wild-type mouse embryonic fibroblast cells does not lead to any significant change in oxidative injury. Loss-of-function studies using sulfiredoxin-depleted A549 and sulfiredoxin -/- cells demonstrate a dramatic increase in extra- and intracellular H2O2, sulfinic 2-Cys peroxiredoxins, and apoptosis. Concomitant with hyperoxidation of mitochondrial peroxiredoxin Prx III, sulfiredoxin-depleted cells show an activation of mitochondria-mediated apoptotic pathways including mitochondria membrane potential collapse, cytochrome c release, and caspase activation |
725510 |
