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Information on EC 1.8.98.2 - sulfiredoxin
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1.8.98.2 sulfiredoxinIUBMB Comments
In the course of the reaction of EC 1.11.1.15, peroxiredoxin, its cysteine residue is alternately oxidized to the sulfenic acid, S-hydroxycysteine, and reduced back to cysteine. Occasionally the S-hydroxycysteine residue is further oxidized to the sulfinic acid S-hydroxy-S-oxocysteine, thereby inactivating the enzyme. The reductase provides a mechanism for regenerating the active form of peroxiredoxin, i.e. the peroxiredoxin-(S-hydroxycysteine) form. Apparently the reductase first catalyses the phosphorylation of the -S(O)-OH group by ATP to give -S(O)-O-P, which is attached to the peroxiredoxin by a cysteine residue, forming an -S(O)-S- link between the two enzymes. Attack by a thiol splits this bond, leaving the peroxiredoxin as the sulfenic acid and the reductase as the thiol.
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Word Map
- 1.8.98.2
- peroxiredoxins
-
hyperoxidation
- thioredoxins
-
overoxidized
-
sulfenic
-
peroxidatic
- txnrd1
-
sulfinylated
-
deglutathionylation
-
prxiii
-
prdxs
-
cys-so2h
- medicine
- drug development
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
sulfiredoxin, srxn1, sulfiredoxin-1, atsrx, sulfiredoxin 1, sulphiredoxin, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
neoplastic progression 3
Srx
Srx1
sulfiredoxin
sulfiredoxin-1
sulphiredoxin
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH = peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
reduction
reduction
ATP-dependent reduction of cysteinesulfinic acid of hyperoxidized peroxiredoxin
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SYSTEMATIC NAME
IUBMB Comments
peroxiredoxin-(S-hydroxy-S-oxocysteine):thiol oxidoreductase [ATP-hydrolysing; peroxiredoxin-(S-hydroxycysteine)-forming]
In the course of the reaction of EC 1.11.1.15, peroxiredoxin, its cysteine residue is alternately oxidized to the sulfenic acid, S-hydroxycysteine, and reduced back to cysteine. Occasionally the S-hydroxycysteine residue is further oxidized to the sulfinic acid S-hydroxy-S-oxocysteine, thereby inactivating the enzyme. The reductase provides a mechanism for regenerating the active form of peroxiredoxin, i.e. the peroxiredoxin-(S-hydroxycysteine) form. Apparently the reductase first catalyses the phosphorylation of the -S(O)-OH group by ATP to give -S(O)-O-P, which is attached to the peroxiredoxin by a cysteine residue, forming an -S(O)-S- link between the two enzymes. Attack by a thiol splits this bond, leaving the peroxiredoxin as the sulfenic acid and the reductase as the thiol.
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CAS REGISTRY NUMBER
COMMENTARY
710319-61-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-Cys peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + GSH
2-Cys peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + GSSG
-
-
-
-
?
overoxidized human peroxiredoxin V + reduced thioredoxin
? + oxidized thioredoxin
Arabidopsis enzyme is able to reduce overoxidized human Prx V
-
-
?
peroxiredoxin IIF-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin IIF-(S-hydroxycysteine) + ADP + phosphate + GSSG
-
-
-
-
?
peroxiredoxin III-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin III-(S-hydroxycysteine) + ADP + phosphate + GSSG
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 DTT
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + DTT disulfide
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + G-S-S-G
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 H2S
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + HS-SH
preference for H2S to support the repair of mitochondrial hyperoxidized Prx3 by Srx. Combined GSH and H2S for the repair of cytosolic Prx2
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + G-S-S-G
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + GSSG
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + thioredoxin 1
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin 1 disulfide
-
-
-
-
r
peroxiredoxin-(S-hydroxy-S-oxocysteine) + dATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + dADP + phosphate + R-S-S-R
-
both glutathione and thioredoxin are potential physiological electron donors
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + dGTP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + GDP + phosphate + R-S-S-R
-
both glutathione and thioredoxin are potential physiological electron donors
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + dGTP + R-SH
peroxiredoxin-(S-hydroxycysteine) + GDP + phosphate + R-S-S-R
-
formation of a covalent thiosulfinate peroxiredoxin-sulfiredoxin species as an intermediate on the catalytic pathway
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + gamma-S-ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + thiophosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + GTP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + GDP + phosphate + R-S-S-R
-
both glutathione and thioredoxin are potential physiological electron donors
-
-
?
sulfinic form of peroxiredoxin IIF + oxidized thioredoxin
? + reduced thioredoxin
in mitochondria, sulfiredoxin catalyzes the retroreduction of the inactive sulfinic form of atypical peroxiredoxin IIF using thioredoxin as reducing agent
-
-
?
sulfinic form of peroxiredoxin IIF + reduced thioredoxin
? + oxidized thioredoxin
in mitochondria, sulfiredoxin catalyzes the retroreduction of the inactive sulfinic form of atypical peroxiredoxin IIF using thioredoxin as reducing agent
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 DTT
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + DTT disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 DTT
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + DTT disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 DTT
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + DTT disulfide
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + G-S-S-G
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + G-S-S-G
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + G-S-S-G
combined GSH and H2S for the repair of cytosolic Prx2
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
r
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
r
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
antioxidant protein with a role in signaling through catalytic reduction of oxidative modifications. Srx also has a role in the reduction of glutathionylation a post-translational, oxidative modification that occurs on numerous proteins and has been implicated in a wide variety of pathologies, including Parkinsons disease. Unlike the reduction of peroxiredoxin overoxidation, Srx-dependent deglutathionylation appears to be nonspecific
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
repairs the inactivated forms of typical two-Cys peroxiredoxins implicated in hydrogen peroxide-mediated cell signaling
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
Srx is largely responsible for reduction of the Cys-SO2H of peroxiredoxin in A549 human cells
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
both glutathione and thioredoxin are potential physiological electron donors
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
the ATP molecule is cleaved between the beta- and gamma-phosphate groups
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
hyperoxidized Prx1
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
reduction of Cys-SO2H by Srx is specific to 2-Cys peroxiredoxin isoforms. For proteins such as Prx VI and GAPDH, sulfinic acid formation might be an irreversible process that causes protein damage
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
r
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
sulphiredoxin is important for the antioxidant function of peroxiredoxins, and is likely to be involved in the repair of proteins containing cysteinesulphinic acid modifications, and in signalling pathways involving protein oxidation
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
the rate-limiting step of the reaction is associated with the chemical process of transfer of the gamma-phosphate of ATP to the sulfinic acid. Two pKapp values of 6.2 and 7.5 of the bell-shaped pH-rate profile correspond to the gamma-phosphate of ATP, and to an acid-base catalyst, respectively
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + GSSG
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + GSSG
identification of intact protein thiosulfinate intermediate in the reduction of cysteine sulfinic acid in peroxiredoxin by human sulfiredoxin
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + GSH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + GSSG
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
AtSrx mutants exhibit an increased tolerance to photooxidative stress generated by high light combined with low temperature
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
additional information
?
-
-
assay conditions optimization, overview
-
-
?
additional information
?
-
-
enzyme is able to act as a redox-dependent sulfinic acid reductase and as a redox-independent nuclease enzyme. Sulfiredoxin functions as a nuclease enzyme that can use single-stranded and double-stranded DNAs as substrates. The active site of the reductase function of sulfiredoxin is not involved in its nuclease function
-
-
?
additional information
?
-
AtSrx has sulfinic acid reductase activity to catalyze the reduction of the overoxidized form of 2-Cys Prx in vitro and in vivo
-
-
-
additional information
?
-
-
AtSrx has sulfinic acid reductase activity to catalyze the reduction of the overoxidized form of 2-Cys Prx in vitro and in vivo
-
-
-
additional information
?
-
AtSrx has sulfinic acid reductase activity to catalyze the reduction of the overoxidized form of 2-Cys Prx in vitro and in vivo. Overall structure of ADP-bound AtSrx, ADP is bound at a positive charged pocket of AtSrx, detailed overview. AtSrx forms a complex with AtPrxA in vitro, modeling
-
-
-
additional information
?
-
-
AtSrx has sulfinic acid reductase activity to catalyze the reduction of the overoxidized form of 2-Cys Prx in vitro and in vivo. Overall structure of ADP-bound AtSrx, ADP is bound at a positive charged pocket of AtSrx, detailed overview. AtSrx forms a complex with AtPrxA in vitro, modeling
-
-
-
additional information
?
-
-
assay conditions optimization, overview
-
-
?
additional information
?
-
-
catalyzes the reduction of cysteine sulfinic acid to sulfenic acid in oxidized proteins and protects them from inactivation
-
-
?
additional information
?
-
-
promotes the reversal of cysteine modified PTP1B to its reduced and enzymatically active form
-
-
?
additional information
?
-
-
reduction of cysteine sulfinic acid to sulfenic acid in proteins subject to oxidative stress
-
-
?
additional information
?
-
Srx forms a complex with the endoplasmic reticulum-resident protein thioredoxin domain-containing protein 5 (TXNDC5) in vivo and in vitro. TXNDC5 directly interacts with Srx through its thioredoxin-like domains, mapping of the interacting domains between Srx and TXNDC5, the thioredoxin-like domains 1 and 3 are responsible for the binding to Srx, overview. Deletion of the first or third thioredoxin-like domain in TXNDC5 results in a significant loss of its binding to Srx, whereas deletion of the second (the one in the middle) thioredoxin-like domain does not compromise its binding to Srx. The Srx-TXNDC5 is a relatively stable complex that is not affected by the treatment with exogenous H2O2
-
-
-
additional information
?
-
-
Srx forms a complex with the endoplasmic reticulum-resident protein thioredoxin domain-containing protein 5 (TXNDC5) in vivo and in vitro. TXNDC5 directly interacts with Srx through its thioredoxin-like domains, mapping of the interacting domains between Srx and TXNDC5, the thioredoxin-like domains 1 and 3 are responsible for the binding to Srx, overview. Deletion of the first or third thioredoxin-like domain in TXNDC5 results in a significant loss of its binding to Srx, whereas deletion of the second (the one in the middle) thioredoxin-like domain does not compromise its binding to Srx. The Srx-TXNDC5 is a relatively stable complex that is not affected by the treatment with exogenous H2O2
-
-
-
additional information
?
-
specificity of human sulfiredoxin for reductant and peroxiredoxin oligomeric state, overview. The resolution of the Prx-Srx complex involves the reduction of the thiosulfinate intermediate (Prx-CP-S=O-S-Srx) to yield the Prx Cys-sulfenic acid intermediate (Prx-CP-SOH). Yeast Srx contains an adjacent resolving Cys residue (Cys-SR) that can react with the thiosulfinate intermediate leading to the formation of an Srx intramolecular disulfide (Srx-(S-S)). In contrast, human Srx has only one Cys residue and requires an exogenous reductant. Possible reductants include the Trx system (Trx/TrxR/NADPH), glutathione (GSH) and hydrogen sulfide (H2S), these reductants would ultimately yield reduced Srx (Srx-SH). Enzyme-substrate binding studies with mutant Prx1 (e.g. Prx1 C83V and Prx1 C71S/C173S). Repair of hyperoxidized Prx2, Prx3 and their chimeras, the C-terminal sequence differences between Prx2 and Prx3 impact the rate of repair by Srx
-
-
-
additional information
?
-
-
specificity of human sulfiredoxin for reductant and peroxiredoxin oligomeric state, overview. The resolution of the Prx-Srx complex involves the reduction of the thiosulfinate intermediate (Prx-CP-S=O-S-Srx) to yield the Prx Cys-sulfenic acid intermediate (Prx-CP-SOH). Yeast Srx contains an adjacent resolving Cys residue (Cys-SR) that can react with the thiosulfinate intermediate leading to the formation of an Srx intramolecular disulfide (Srx-(S-S)). In contrast, human Srx has only one Cys residue and requires an exogenous reductant. Possible reductants include the Trx system (Trx/TrxR/NADPH), glutathione (GSH) and hydrogen sulfide (H2S), these reductants would ultimately yield reduced Srx (Srx-SH). Enzyme-substrate binding studies with mutant Prx1 (e.g. Prx1 C83V and Prx1 C71S/C173S). Repair of hyperoxidized Prx2, Prx3 and their chimeras, the C-terminal sequence differences between Prx2 and Prx3 impact the rate of repair by Srx
-
-
-
additional information
?
-
Srx transfers the gamma-phosphate of ATP to Cp sulfinic acid on hyperoxidized Prxs and produces sulfinic phosphoryl ester. Subsequent involvement of GSH and thioredoxin will ensure the reduction of sulfinic phosphoryl ester to sulfenic acid
-
-
-
additional information
?
-
-
Srx transfers the gamma-phosphate of ATP to Cp sulfinic acid on hyperoxidized Prxs and produces sulfinic phosphoryl ester. Subsequent involvement of GSH and thioredoxin will ensure the reduction of sulfinic phosphoryl ester to sulfenic acid
-
-
-
additional information
?
-
-
catalyzes the reduction of cysteine sulfinic acid to sulfenic acid in oxidized proteins and protects them from inactivation
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
antioxidant protein with a role in signaling through catalytic reduction of oxidative modifications. Srx also has a role in the reduction of glutathionylation a post-translational, oxidative modification that occurs on numerous proteins and has been implicated in a wide variety of pathologies, including Parkinsons disease. Unlike the reduction of peroxiredoxin overoxidation, Srx-dependent deglutathionylation appears to be nonspecific
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
repairs the inactivated forms of typical two-Cys peroxiredoxins implicated in hydrogen peroxide-mediated cell signaling
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
Srx is largely responsible for reduction of the Cys-SO2H of peroxiredoxin in A549 human cells
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
reduction of Cys-SO2H by Srx is specific to 2-Cys peroxiredoxin isoforms. For proteins such as Prx VI and GAPDH, sulfinic acid formation might be an irreversible process that causes protein damage
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
sulphiredoxin is important for the antioxidant function of peroxiredoxins, and is likely to be involved in the repair of proteins containing cysteinesulphinic acid modifications, and in signalling pathways involving protein oxidation
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + 2 thioredoxin
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + thioredoxin disulfide
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
AtSrx mutants exhibit an increased tolerance to photooxidative stress generated by high light combined with low temperature
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
peroxiredoxin-(S-hydroxy-S-oxocysteine) + ATP + R-SH
peroxiredoxin-(S-hydroxycysteine) + ADP + phosphate + R-S-S-R
-
-
-
-
?
additional information
?
-
AtSrx has sulfinic acid reductase activity to catalyze the reduction of the overoxidized form of 2-Cys Prx in vitro and in vivo
-
-
-
additional information
?
-
-
AtSrx has sulfinic acid reductase activity to catalyze the reduction of the overoxidized form of 2-Cys Prx in vitro and in vivo
-
-
-
additional information
?
-
-
catalyzes the reduction of cysteine sulfinic acid to sulfenic acid in oxidized proteins and protects them from inactivation
-
-
?
additional information
?
-
Srx forms a complex with the endoplasmic reticulum-resident protein thioredoxin domain-containing protein 5 (TXNDC5) in vivo and in vitro. TXNDC5 directly interacts with Srx through its thioredoxin-like domains, mapping of the interacting domains between Srx and TXNDC5, the thioredoxin-like domains 1 and 3 are responsible for the binding to Srx, overview. Deletion of the first or third thioredoxin-like domain in TXNDC5 results in a significant loss of its binding to Srx, whereas deletion of the second (the one in the middle) thioredoxin-like domain does not compromise its binding to Srx. The Srx-TXNDC5 is a relatively stable complex that is not affected by the treatment with exogenous H2O2
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-
-
additional information
?
-
-
Srx forms a complex with the endoplasmic reticulum-resident protein thioredoxin domain-containing protein 5 (TXNDC5) in vivo and in vitro. TXNDC5 directly interacts with Srx through its thioredoxin-like domains, mapping of the interacting domains between Srx and TXNDC5, the thioredoxin-like domains 1 and 3 are responsible for the binding to Srx, overview. Deletion of the first or third thioredoxin-like domain in TXNDC5 results in a significant loss of its binding to Srx, whereas deletion of the second (the one in the middle) thioredoxin-like domain does not compromise its binding to Srx. The Srx-TXNDC5 is a relatively stable complex that is not affected by the treatment with exogenous H2O2
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-
additional information
?
-
-
catalyzes the reduction of cysteine sulfinic acid to sulfenic acid in oxidized proteins and protects them from inactivation
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(((4-(4-(2-chlorophenyl)piperazin-1-yl)-6-(2,4-dihydroxy-5-isopropylphenyl)pyrimidin-2-yl)thio)methyl)benzoic acid
LMT-328, synthesis, a derivative of Jl4, more potent inhibitor than J14. The simulation, LMT-328 shows fast stabilization and tight binding with Srx. LMT-328 has a similar binding pose as the lead compound, J14, overview
-
4-[[[4-[4-(2-chlorophenyl)-1-piperazinyl]-6-phenyl-2-pyrimidinyl]thio]methyl]-benzoic acid
J14, synthesis, interferes with the antioxidant activity of Srx at the molecular level. Identification of two possible inhibition mechanisms of Srx by J14. Using molecular dynamics simulations and binding free energy calculations, it is confirmed that J14 binds to the ATP binding site, J14 acts as a competitive inhibitor of ATP. J14 can serve as a protein-protein interaction inhibitor that interferes with the binding between Prx and Srx
-
additional information
-
screening for Srx inhibitors is carried out in an automated setup using 25000 chemicals
-
additional information
analysis of the inhibition mechanism of sulfiredoxin using molecular modeling and development of its inhibitors. Protein-ligand docking simulation of J14 and LMT-328, molecular dynamics simulation and binding free energy calculation, elucidation of the Srx inhibition mechanism, detailed overview
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma.
Adenocarcinoma
Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer.
Brain Injuries
Sulfiredoxin-1 Attenuates Oxidative Stress via Nrf2/ARE Pathway and 2-Cys Prdxs After Oxygen-Glucose Deprivation in Astrocytes.
Brain Ischemia
Neuroprotective effects of sulfiredoxin-1 during cerebral ischemia/reperfusion oxidative stress injury in rats.
Brain Ischemia
Sulfiredoxin-1 exerts anti-apoptotic and neuroprotective effects against oxidative stress-induced injury in rat cortical astrocytes following exposure to oxygen-glucose deprivation and hydrogen peroxide.
Breast Neoplasms
Correction: Genetic Polymorphisms and Protein Expression of NRF2 and Sulfiredoxin Predict Survival Outcomes in Breast Cancer.
Breast Neoplasms
Genetic polymorphisms and protein expression of NRF2 and sulfiredoxin predict survival outcomes in breast cancer.
Breast Neoplasms
Maesopsin 4-O-beta-D-glucoside, a natural compound isolated from the leaves of Artocarpus tonkinensis, inhibits proliferation and up-regulates HMOX1, SRXN1 and BCAS3 in acute myeloid leukemia.
Carcinogenesis
Loss of sulfiredoxin renders mice resistant to azoxymethane/dextran sulfate sodium-induced colon carcinogenesis.
Carcinogenesis
Nrf2-activated expression of sulfiredoxin contributes to urethane-induced lung tumorigenesis.
Carcinogenesis
SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling.
Carcinogenesis
Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling.
Carcinogenesis
Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis.
Carcinoma
Nuclear factor erythroid-derived 2-like 2 (Nrf2) and DJ1 are prognostic factors in lung cancer.
Carcinoma
Sulfiredoxin may promote metastasis and invasion of cervical squamous cell carcinoma by epithelial-mesenchymal transition.
Carcinoma
[Highly expressed sulfiredoxin and ?-catenin are associated with malignancy of cervical squamous cell carcinoma].
Carcinoma, Hepatocellular
SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling.
Carcinoma, Hepatocellular
Sulfiredoxin-1 is a promising novel prognostic biomarker for hepatocellular carcinoma.
Carcinoma, Squamous Cell
Sulfiredoxin may promote metastasis and invasion of cervical squamous cell carcinoma by epithelial-mesenchymal transition.
Carcinoma, Squamous Cell
[Highly expressed sulfiredoxin and ?-catenin are associated with malignancy of cervical squamous cell carcinoma].
Cerebral Infarction
Neuroprotective effects of sulfiredoxin-1 during cerebral ischemia/reperfusion oxidative stress injury in rats.
Cerebrovascular Disorders
Genetic Polymorphisms of Transcription Factor NRF2 and of its Host Gene Sulfiredoxin (SRXN1) are Associated with Cerebrovascular Disease in a Finnish Cohort, the TAMRISK Study.
Chronic Periodontitis
Comparative estimation of sulfiredoxin levels between chronic periodontitis and healthy patients - A case-control study.
Colorectal Neoplasms
Sulfiredoxin Promotes Colorectal Cancer Cell Invasion and Metastasis through a Novel Mechanism of Enhancing EGFR Signaling.
Diabetic Nephropathies
Sulfiredoxin-1 alleviates high glucose-induced podocyte injury though promoting Nrf2/ARE signaling via inactivation of GSK-3?.
Hypersensitivity
Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons.
Hypertension
Genetic Polymorphisms of Transcription Factor NRF2 and of its Host Gene Sulfiredoxin (SRXN1) are Associated with Cerebrovascular Disease in a Finnish Cohort, the TAMRISK Study.
Idiopathic Pulmonary Fibrosis
Cell-specific elevation of NRF2 and sulfiredoxin-1 as markers of oxidative stress in the lungs of idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.
Infarction, Middle Cerebral Artery
Neuroprotective effects of sulfiredoxin-1 during cerebral ischemia/reperfusion oxidative stress injury in rats.
Ischemic Stroke
Neuroprotective effects of sulfiredoxin-1 during cerebral ischemia/reperfusion oxidative stress injury in rats.
Leukemia, Myeloid, Acute
Maesopsin 4-O-beta-D-glucoside, a natural compound isolated from the leaves of Artocarpus tonkinensis, inhibits proliferation and up-regulates HMOX1, SRXN1 and BCAS3 in acute myeloid leukemia.
Lung Diseases, Interstitial
Cell-specific elevation of NRF2 and sulfiredoxin-1 as markers of oxidative stress in the lungs of idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.
Lung Neoplasms
Nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer.
Lung Neoplasms
Nuclear factor erythroid-derived 2-like 2 (Nrf2) and DJ1 are prognostic factors in lung cancer.
Lung Neoplasms
The redox regulator sulfiredoxin forms a complex with thioredoxin domain-containing 5 protein in response to ER stress in lung cancer cells.
Melanoma
Frugoside Induces Mitochondria-Mediated Apoptotic Cell Death through Inhibition of Sulfiredoxin Expression in Melanoma Cells.
Meningoencephalitis
Sulfiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signaling pathway in Cryptococcus neoformans and contributes to fungal virulence.
Myocardial Ischemia
Sulfiredoxin-1 enhances cardiac progenitor cell survival against oxidative stress via the upregulation of the ERK/NRF2 signal pathway.
Neoplasm Metastasis
SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling.
Neoplasm Metastasis
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/?-Catenin Signaling Pathway.
Neoplasm Metastasis
Sulfiredoxin may promote metastasis and invasion of cervical squamous cell carcinoma by epithelial-mesenchymal transition.
Neoplasm Metastasis
Sulfiredoxin Promotes Colorectal Cancer Cell Invasion and Metastasis through a Novel Mechanism of Enhancing EGFR Signaling.
Neoplasms
Effective killing of cancer cells and regression of tumor growth by K27 targeting sulfiredoxin.
Neoplasms
Elucidation of the inhibition mechanism of sulfiredoxin using molecular modeling and development of its inhibitors.
Neoplasms
Identification and characterization of human leukocyte antigen class I ligands in renal cell carcinoma cells.
Neoplasms
Nuclear factor erythroid-derived 2-like 2 (Nrf2) and DJ1 are prognostic factors in lung cancer.
Neoplasms
SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling.
Neoplasms
Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer.
Neoplasms
Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage.
Neoplasms
Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies.
Neoplasms
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/?-Catenin Signaling Pathway.
Neoplasms
Sulfiredoxin may promote metastasis and invasion of cervical squamous cell carcinoma by epithelial-mesenchymal transition.
Neoplasms
Sulfiredoxin redox-sensitive interaction with S100A4 and non-muscle myosin IIA regulates cancer cell motility.
Neoplasms
Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling.
Neoplasms
The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth.
Neoplasms
Thioredoxin system-mediated regulation of mutant Kras associated pancreatic neoplasia and cancer.
Neoplasms
[Highly expressed sulfiredoxin and ?-catenin are associated with malignancy of cervical squamous cell carcinoma].
Neurodegenerative Diseases
Role of sulfiredoxin as a peroxiredoxin-2 denitrosylase in human iPSC-derived dopaminergic neurons.
Neurodegenerative Diseases
Sulfiredoxin-1 protects primary cultured astrocytes from ischemia-induced damage.
Pancreatic Neoplasms
Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma.
Pancreatitis
Sulfiredoxin-1 attenuates injury and inflammation in acute pancreatitis through the ROS/ER stress/Cathepsin B axis.
Periodontal Diseases
Comparative estimation of sulfiredoxin levels between chronic periodontitis and healthy patients - A case-control study.
Periodontitis
Comparative estimation of sulfiredoxin levels between chronic periodontitis and healthy patients - A case-control study.
Prostatic Intraepithelial Neoplasia
Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer.
Prostatic Neoplasms
Increased Peroxiredoxin 6 Expression Predicts Biochemical Recurrence in Prostate Cancer Patients After Radical Prostatectomy.
Prostatic Neoplasms
Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer.
Pulmonary Disease, Chronic Obstructive
The aryl hydrocarbon receptor suppresses cigarette-smoke-induced oxidative stress in association with dioxin response element (DRE)-independent regulation of sulfiredoxin 1.
Skin Neoplasms
Tumor promoter-induced sulfiredoxin is required for mouse skin tumorigenesis.
Stomach Neoplasms
Increased Sulfiredoxin Expression in Gastric Cancer Cells May Be a Molecular Target of the Anticancer Component Diallyl Trisulfide.
Uterine Cervical Neoplasms
Sulfiredoxin May Promote Cervical Cancer Metastasis via Wnt/?-Catenin Signaling Pathway.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetic analysis, overview
-
0.029
peroxiredoxin-(S-hydroxy-S-oxocysteine)
-
pH 7.5, 30°C, saturating ATP, 0.03 mM Srx, 0.04 mM substrate
0.079
peroxiredoxin-(S-hydroxy-S-oxocysteine)
-
pH 7.5, 30°C, 1 mM ATP, 0.03 mM Srx, saturating substrate concentration
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00042
peroxiredoxin-(S-hydroxy-S-oxocysteine)
-
pH 7.5, 30°C, saturating ATP, 0.03 mM Srx, 0.04 mM substrate
0.011
peroxiredoxin-(S-hydroxy-S-oxocysteine)
-
pH 7.5, 30°C, 1 mM ATP, 0.03 mM Srx, saturating substrate concentration
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0067
4-(((4-(4-(2-chlorophenyl)piperazin-1-yl)-6-(2,4-dihydroxy-5-isopropylphenyl)pyrimidin-2-yl)thio)methyl)benzoic acid
Homo sapiens
against A549 cells, pH and temperature not specified in the publication
-
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
9.86
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
cortical glial cell, in both neurons and glia, Nrf2 expression and treatment with chemopreventive Nrf2 activators, including 3H-1,2-dithiole-3-thione and sulforaphane, upregulate sulfiredoxin, an enzyme responsible for reducing hyperoxidized peroxiredoxins
brenda
Srx is highly expressed in primary specimen of lung cancer patients
brenda
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cortical neuron, in both neurons and glia, Nrf2 expression and treatment with chemopreventive Nrf2 activators, including 3H-1,2-dithiole-3-thione and sulforaphane, upregulate sulfiredoxin, an enzyme responsible for reducing hyperoxidized peroxiredoxins
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
colocalization of Srx and TXNDC5 in endoplasmic reticulum of cultured cells
brenda
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Srx possesses a chloroplast transit peptide in the N-terminus
brenda
residues 1-22 of AtSrx are predicted as a chloroplast-targeting transit peptide
brenda
-
Srx possesses a chloroplast transit peptide in the N-terminus
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brenda
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cytosolic Srx is translocated into the mitochondria under oxidative conditions
brenda
dual localization to plastid and mitochondrion, in line with the prediction of a signal peptide for dual targeting. In mitochondria, enzyme interacts with peroxiredoxin IIF and thioredoxin. Sulfiredoxin catalyzes the retroreduction of the inactive sulfinic form of atypical Prx IIF using thioredoxin as reducing agent
brenda
dual localization to plastid and mitochondrion, in line with the prediction of a signal peptide for dual targeting. In mitochondria, enzyme interacts with peroxiredoxin IIF and thioredon. Sulfiredoxin catalyzes the retroreduction of the inactive sulfinic form of atypical Prx IIF using thioredoxin as reducing agent
brenda
dual localization to plastid and mitochondrion, in line with the prediction of a signal peptide for dual targeting
brenda
dual localization to plastid and mitochondrion, in line with the prediction of a signal peptide for dual targeting
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
malfunction
physiological function
additional information
malfunction
inhibition of sulfiredoxin (Srx), which participates in antioxidant mechanisms, induces ROS-mediated cancer cell death
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
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
physiological function
-
the antioxidant function of 2-Cys peroxiredoxin, Prx, EC 1.11.1.15, involves the oxidation of its conserved peroxidatic cysteine to sulfinic acid that is recycled by a reductor agent. Sulfiredoxin reduces the sulfinic 2-Cys Prx, Prx-SO2H. The activity of sulfiredoxin is dependent on the concentration of the sulfinic form of Prx and the conserved Srx is capable of regenerating the functionality of both pea and Arabidopsis Prx-SO2H
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
physiological function
-
sulfiredoxin Srx1 reactivates the yeast peroxiredoxin Prx1 peroxidase activity that is inactivated by H2O2, whereas it decreases the chaperone activity enhanced by H2O2. Srx1 dissociates the H2O2-induced high molecular weight Prx1 complex, and the Srx1 Cys84 residue is critical for its dissociation
physiological function
-
enzyme induction is the pivotal compensatory protection mechanism against oxidative stress in diabetes or hyperglycaemia
physiological function
-
mitochondrial H2O2 signaling is controlled by the concerted action of peroxiredoxin III and sulfiredoxin
physiological function
-
sulfiredoxin-1 protects PC-12 cells against oxidative stress induced by hydrogen peroxide
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
physiological function
Prxs, a type of the antioxidant peroxidases in cells, are including thioredoxin- and sulfiredoxin-dependent peroxidases, which play a crucial role in decreasing ROS levels in cells by taking part in the catalytic cycle. During the catalytic cycle for the reduction of Prx, a Cys active site residue (Cys-SH) of Prx is oxidized to a cysteine sulfenic acid (Cys-SOH) after forming a disulfide bond with the other cysteine of the adjacent Prx monomer. The oxidized Prx is reduced back to the initial form by thioredoxin (Trx). Moreover, the oxidized cysteine of Prx (Cys-SOH) can be oxidized again into sulfinic acid (Cys-SO2H). Srx exclusively reduces sulfinic acid to sulfenic acid by an ATP-dependent reaction catalyzed in presence of Mg2+. Antioxidant peroxidases, including Prx and Srx, are abundantly expressed in various cancers cells, and cancer cells are known to be more vulnerable to the toxicity of ROS under oxidative stress conditions than normal cells
physiological function
Sulfiredoxin (Srx) reduces hyperoxidized 2-cysteine-containing peroxiredoxins (Prxs) and protects cells against oxidative stress. Cellular peroxidases, including Prxs, are antioxidant enzymes that contribute to the development of lung cancer. Srx is highly expressed in primary specimens of lung cancer patients and plays a pivotal role in lung tumorigenesis and cancer progression. Srx has an oncogenic function that promotes the invasion and metastasis of lung cancer cells. In response to ER stress but not to oxidative stress, Srx exhibits an increased association with the endoplasmic reticulum (ER)-resident protein thioredoxin domain-containing protein 5 (TXNDC5), facilitating the retention of Srx in the ER. The overall amounts of TXNDC5 associated with Srx are not affected by the exposure of cells to exogenous H2O2 as high as 1 mM, functional significance of Srx and TXNDC5 at different stages of lung cancer. Of note, TXNDC5 knockdown in lung cancer cells inhibits cell proliferation and represses anchorage-independent colony formation and migration, but increases cell invasion and activation of mitogen-activated protein kinases. Expression of TXNDC5 stimulates anchorage-independent colony formation but inhibits cell invasion. Knockdown of TXNDC5 enhances EGF-induced MAPK activation. TXNDC5 is highly expressed in patient-derived lung cancer specimen. Patients with high Srx levels have significantly shorter survival and those with high TXNDC5 levels have longer survival. The function of Srx appears to be necessary to maintain the redox balance in cancer cells
physiological function
the repair and reactivation of the hyperoxidized Prxs by Srx is an important cellular process, hydrogen sulfide repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx), structural requirements, peroxiredoxin catalytic and sulfiredoxin repair cycles, detailed overview. The physiological reductants hydrogen sulfide (H2S) and glutathione (GSH) show relative efficacy in this reaction. Prx isoform-dependent use of and potential cooperation between GSH and H2S in supporting Srx activity
physiological function
-
the antioxidant function of 2-Cys peroxiredoxin, Prx, EC 1.11.1.15, involves the oxidation of its conserved peroxidatic cysteine to sulfinic acid that is recycled by a reductor agent. Sulfiredoxin reduces the sulfinic 2-Cys Prx, Prx-SO2H. The activity of sulfiredoxin is dependent on the concentration of the sulfinic form of Prx and the conserved Srx is capable of regenerating the functionality of both pea and Arabidopsis Prx-SO2H
-
additional information
Cys99 of Srx is critical for its catalytic activity
additional information
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
additional information
-
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
additional information
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
additional information
-
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
Show AA Sequence and Transmembrane Helices (1793 entries)
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Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
11546
-
x * 13914, immature enzyme, sequence calculation, x * 11546, mature enzyme, sequence calculation
13914
-
x * 13914, immature enzyme, sequence calculation, x * 11546, mature enzyme, sequence calculation
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
-
x * 13914, immature enzyme, sequence calculation, x * 11546, mature enzyme, sequence calculation
?
-
x * 13914, immature enzyme, sequence calculation, x * 11546, mature enzyme, sequence calculation
-
additional information
the decameric Srx-Prx1 complex reveals extended binding interface, human Prx1 and Prx2 form a decameric toroid
additional information
-
the decameric Srx-Prx1 complex reveals extended binding interface, human Prx1 and Prx2 form a decameric toroid
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme AtSrx in complex with ADP, sitting drop vapor diffusion method, mixing of 0.001 ml of 20 mg/ml protein in 50 mM Tris-HCl, pH 7.5, 50 mM NaCl, and 1 mM DTT, with 0.001 ml of well solution containing 0.8 M NaH2PO4/1.2M KH2PO4, and acetate, pH 4.5, at 16°C, 1 week, X-ray diffraction structure determination and analysis at 3.20 A resolution
crystals of the wild-type and SeMet forms of ET-hSrx were obtained by the vapor diffusion method. 1.65 A crystal structure of human Srx
purified Srx-Prx1 complex, hanging drop vapor diffusion method, mixing of 10 mg/ml protein in 20 mM HEPES, pH 7.5, 100 mM NaCl with well solution containing 100 mM citric acid, pH 4.5, 26% PEG 400, and 100 mM CsCl, X-ray diffraction structure determination and analysis at 3.0 A resolution, molecular replacement and modeling by superimposing five dimeric Srx-Prx1 complexes (PDB entry 2RII) onto the five Prx dimers within the decameric Prx2-SO2H (PDB ID 1QMV) structure. The entire active site helix of Prx1 (residues 46-69) and the C-terminus (residues 169-199) are removed from the search model to reduce bias. Two decamers, each containing ten Prx and ten Srx molecules (five Prx dimers and ten Srx monomers), are found in the asymmetric unit, consistent with the observed self-rotation function. Additional crystallization of hyperoxidized Prx2 and Prx3 variants
vapour diffusion method, 2.6 A crystal structure of the sulphiredoxinperoxiredoxin-I complex
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C72S
E76A
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
K40Q
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-type enzyme
R28Q
R28Q/E76A
C72S
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-type enzyme
-
E76A
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
-
R28Q
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-type enzyme
-
C99A
C99S
C106A
-
mutant, constructed to address questions regarding the catalytic mechanisms and the role of the cysteine residues
C48A
-
mutant, constructed to address questions regarding the catalytic mechanisms and the role of the cysteine residues
C48A/C106A
-
mutant, constructed to address questions regarding the catalytic mechanisms and the role of the cysteine residues
C84S
-
Srx1 reactivates the yeast Prx1 peroxidase activity that is inactivated by H2O2. Mutant C84S does not induce the reactivation of inactivated Prx1 or dissociation of the high molecular weight Prx1 complex
additional information
C72S
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-type enzyme
C72S
-
loss of sulfinate reductase activity, no effect on DNA binding and hydrolizing activities
C72S
site-directed mutagenesis, the cysteine-deficient mutation at the active completely abolishes activity of Srx
R28Q
-
site-directed mutagenesis, the mutant shows decreased activity compared to the wild-type enzyme
R28Q
site-directed mutagenesis, the mutation in AtSrx only partially reduces its activity and needs the additional mutation of E76 to totally inactivation. The survived activity of AtSrx may be the result of that AtSrx has two more arginine residues at the loop next to alpha1. The side chains of Arg32 and Arg34, which can swing to the side of Cys72, may partially compensate for the effects of the loss of Arg28
R28Q/E76A
site-directed mutagenesis, the double mutation disrupts the stability of the loop in which Arg32/Arg34 is located, therefore AtSrx is completely inactivated
C99A
site-directed mutagenesis, the mutation leads to a complete loss of both Srx enzymatic activity and binding to substrates such as Prxs
C99S
mutant created to show the importance of the cytosine residue in the deglutathionylation function of the protein
additional information
-
construction of a Srx knockout mutant, phenotype, overview
additional information
-
construction of a Srx knockout mutant, phenotype, overview
-
additional information
several lentiviral shRNAs targeting separate coding regions of Srx mRNA (shSrx) are used to knockdown the levels of endogenously expressed protein. Two shRNAs targeting the coding regions of TXNDC5 have the highest efficiency to inhibit the expression of endogenous protein. These shRNAs are introduced into A549 and H226 cells by viral infection. Enzyme knockdown in in stable A-549 or H-226 cells expressing shSrx1 or shSrx2. Knockdown of Srx leads to a rapid activation of the unfolded protein response (UPR) and sensitizes human lung cancer cells to ER stress-induced cell death
additional information
-
several lentiviral shRNAs targeting separate coding regions of Srx mRNA (shSrx) are used to knockdown the levels of endogenously expressed protein. Two shRNAs targeting the coding regions of TXNDC5 have the highest efficiency to inhibit the expression of endogenous protein. These shRNAs are introduced into A549 and H226 cells by viral infection. Enzyme knockdown in in stable A-549 or H-226 cells expressing shSrx1 or shSrx2. Knockdown of Srx leads to a rapid activation of the unfolded protein response (UPR) and sensitizes human lung cancer cells to ER stress-induced cell death
additional information
Srx mutant variants analyzed by circular dichroism spectroscopy (JASCO-720) in 20 mM HEPES, pH 7.5, 100 mM NaCl at a concentration from 0.4 mg/ml are confirmed to exhibit wild-type-like spectra
additional information
-
Srx mutant variants analyzed by circular dichroism spectroscopy (JASCO-720) in 20 mM HEPES, pH 7.5, 100 mM NaCl at a concentration from 0.4 mg/ml are confirmed to exhibit wild-type-like spectra
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
His-Srx proteins are purified from cell lysates by chromatography on a column on Ni-chelating Sepharose
-
recombinant His-tagged full-length enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, ultrafiltration, and gel filtration
recombinant wild-type Srx and mutants to homogeneity from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression of N-terminally His6-tagged wild-type Srx and mutants in Escherichia coli strain BL21(DE3)
-
expressed in Saccharomyces cerevisiae
expression in Escherichia coli
gene SRX, overexpression of recombinant His-tagged full-length enzyme in Escherichia coli strain BL21(DE3)
the 5' flanking region of the human Srx1 promoter region, -3664 - +19, is ligated into the vector pCR2.1
-
the vectors pcDNA3 and pFLAG-CMV2 are used, a leader sequence is cloned into the N-terminus coding region of Srx
-
transient expression of an AtSrx-GFP fusion in Nicotiana tabacum leaves
transient recombinant expression of the FLAG-tagged enzyme in different cell types, including HEK293T, H226, and A549 cells, recombinant expression of FLAG-tagged Srx mutant C99A mutant in HEK-293T cells. The Srx-protein complex is pulled down by anti-FLAG immunoprecipitation (IP), and protein identities are determined by mass spectrometry. Among the handful of proteins identified, Prx4 is the most abundant protein, and TXNDC5 is the second most abundant protein that is specifically pulled down by anti-FLAG IP in all cell types. c-Myc-tagged TXNDC5 or its cysteine-specific mutants are expressed in HEK-293T-FLAG-Srx cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
adrenocortical tumor cell lines show increased enzyme expression. Adrenocorticotropic hormone also induces upregulation of the enzyme with its levels peaking at 3-6 h after injection of adrenocorticotropic hormone
-
disruption of Nrf2 signaling down-regulates the expression of Srx1
Nrf2, nuclear factor erythroid-2-related factor, up-regulates Srx1 expression during oxidative stress caused by cigarette smoke exposure in the lungs
oxidative stress and growth factors can markedly upregulate Srx transcript and protein levels
-
under the oxidation stress elicited by hydrogen peroxide, the transcription level of AtSrx is significantly increased
Nrf2, nuclear factor erythroid-2-related factor, up-regulates Srx1 expression during oxidative stress caused by cigarette smoke exposure in the lungs
-
Nrf2, nuclear factor erythroid-2-related factor, up-regulates Srx1 expression during oxidative stress caused by cigarette smoke exposure in the lungs
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
the lung cancer patients with high Srx levels have significantly shorter survival and those with high TXNDC5 levels have longer survival. Cellular levels of Srx and TXNDC5 may be useful as biomarkers to predict the survival of individuals with lung cancer
drug development
-
Srx may be a potential target for prevention or treatment of cancer, the colorimetric assay would be useful for high-throughput screening of Srx inhibitors as demonstrated
medicine
medicine
-
increased sulfiredoxin has been linked with oncogenic transformation, data support a role for Srx in controlling the phosphorylation status of key regulatory kinases
medicine
-
oxidative stress results in protein oxidation and is involved in the pathogenesis of lung diseases such as chronic obstructive pulmonary disorder, COPD, in lungs from COPD patients the expression of Srx1 is dramatically decreased
medicine
-
oxidative stress results in protein oxidation and is involved in the pathogenesis of lung diseases such as chronic obstructive pulmonary disorder, COPD, in lungs from COPD patients the expression of Srx1 is dramatically decreased
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jnsson, T.J.; Murray, M.S.; Johnson, L.C.; Poole, L.B.; Lowther, W.T.
Structural basis for the retroreduction of inactivated peroxiredoxins by human sulfiredoxin
Biochemistry
44
8634-8642
2005
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Findlay, V.J.; Tapiero, H.; Townsend, D.M.
Sulfiredoxin: a potential therapeutic agent?
Biomed. Pharmacother.
59
374-379
2005
Homo sapiens
brenda
Chang, T.S.; Jeong, W.; Woo, H.A.; Lee, S.M.; Park, S.; Rhee, S.G.
Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine
J. Biol. Chem.
279
50994-51001
2004
Homo sapiens, Mus musculus, Rattus norvegicus
brenda
Woo, H.A.; Jeong, W.; Chang, T.S.; Park, K.J.; Park, S.J.; Yang, J.S.; Rhee, S.G.
Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-Cys peroxiredoxins
J. Biol. Chem.
280
3125-3128
2005
Rattus norvegicus
brenda
Biteau, B.; Labarre, J.; Toledano, M.B.
ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin
Nature
425
980-984
2003
Saccharomyces cerevisiae
brenda
Lee, D.Y.; Park, S.J.; Jeong, W.; Sung, H.J.; Oho, T.; Wu, X.; Rhee, S.G.; Gruschus, J.M.
Mutagenesis and modeling of the peroxiredoxin (Prx) complex with the NMR structure of ATP-bound human sulfiredoxin implicate aspartate 187 of Prx I as the catalytic residue in ATP hydrolysis
Biochemistry
45
15301-15309
2006
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Findlay, V.J.; Townsend, D.M.; Morris, T.E.; Fraser, J.P.; He, L.; Tew, K.D.
A novel role for human sulfiredoxin in the reversal of glutathionylation
Cancer Res.
66
6800-6806
2006
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Liu, X.P.; Liu, X.Y.; Zhang, J.; Xia, Z.L.; Liu, X.; Qin, H.J.; Wang, D.W.
Molecular and functional characterization of sulfiredoxin homologs from higher plants
Cell Res.
16
287-296
2006
Oryza sativa, Arabidopsis thaliana (Q8GY89)
brenda
Jeong, W.; Park, S.J.; Chang, T.S.; Lee, D.Y.; Rhee, S.G.
Molecular mechanism of the reduction of cysteine sulfinic acid of peroxiredoxin to cysteine by mammalian sulfiredoxin
J. Biol. Chem.
281
14400-14407
2006
Homo sapiens
brenda
Jang, H.H.; Chi, Y.H.; Park, S.K.; Lee, S.S.; Lee, J.R.; Park, J.H.; Moon, J.C.; Lee, Y.M.; Kim, S.Y.; Lee, K.O.; Lee, S.Y.
Structural and functional regulation of eukaryotic 2-Cys peroxiredoxins including the plant ones in cellular defense-signaling mechanisms against oxidative stress
Physiol. Plant.
126
549-559
2006
Saccharomyces cerevisiae, Homo sapiens
brenda
Rey, P.; Becuwe, N.; Barrault, M.B.; Rumeau, D.; Havaux, M.; Biteau, B.; Toledano, M.B.
The Arabidopsis thaliana sulfiredoxin is a plastidic cysteine-sulfinic acid reductase involved in the photooxidative stress response
Plant J.
49
505-514
2007
Arabidopsis thaliana, Arabidopsis thaliana (Q8GY89)
brenda
Roussel, X.; Bechade, G.; Kriznik, A.; Van Dorsselaer, A.; Sanglier-Cianferani, S.; Branlant, G.; Rahuel-Clermont, S.
Evidence for the formation of a covalent thiosulfinate intermediate with peroxiredoxin in the catalytic mechanism of sulfiredoxin
J. Biol. Chem.
283
22371-22382
2008
Saccharomyces cerevisiae
brenda
Joensson, T.J.; Tsang, A.W.; Lowther, W.T.; Furdui, C.M.
Identification of intact protein thiosulfinate intermediate in the reduction of cysteine sulfinic acid in peroxiredoxin by human sulfiredoxin
J. Biol. Chem.
283
22890-22894
2008
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Soriano, F.X.; Leveille, F.; Papadia, S.; Higgins, L.G.; Varley, J.; Baxter, P.; Hayes, J.D.; Hardingham, G.E.
Induction of sulfiredoxin expression and reduction of peroxiredoxin hyperoxidation by the neuroprotective Nrf2 activator 3H-1,2-dithiole-3-thione
J. Neurochem.
107
533-543
2008
Rattus norvegicus
brenda
Joensson, T.J.; Johnson, L.C.; Lowther, W.T.
Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace
Nature
451
98-101
2008
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Kim, H.; Kim, H.; Hong, S.; Rhee, S.G.; Jeong, W.
A colorimetric assay for sulfiredoxin activity using inorganic phosphate measurement
Anal. Biochem.
393
36-40
2009
Homo sapiens
brenda
Singh, A.; Ling, G.; Suhasini, A.N.; Zhang, P.; Yamamoto, M.; Navas-Acien, A.; Cosgrove, G.; Tuder, R.M.; Kensler, T.W.; Watson, W.H.; Biswal, S.
Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs
Free Radic. Biol. Med.
46
376-386
2009
Homo sapiens, Mus musculus
brenda
Park, J.W.; Mieyal, J.J.; Rhee, S.G.; Chock, P.B.
Deglutathionylation of 2-Cys peroxiredoxin is specifically catalyzed by sulfiredoxin
J. Biol. Chem.
284
23364-23374
2009
Homo sapiens
brenda
Roussel, X.; Kriznik, A.; Richard, C.; Rahuel-Clermont, S.; Branlant, G.
The catalytic mechanism of Sulfiredoxin from Saccharomyces cerevisiae passes through an oxidized disulfide Sulfiredoxin intermediate that is reduced by thioredoxin
J. Biol. Chem.
284
33048-33055
2009
Saccharomyces cerevisiae
brenda
Noh, Y.H.; Baek, J.Y.; Jeong, W.; Rhee, S.G.; Chang, T.S.
Sulfiredoxin Translocation into Mitochondria Plays a Crucial Role in Reducing Hyperoxidized Peroxiredoxin III
J. Biol. Chem.
284
8470-8477
2009
Homo sapiens
brenda
Lei, K.; Townsend, D.M.; Tew, K.D.
Protein cysteine sulfinic acid reductase (sulfiredoxin) as a regulator of cell proliferation and drug response
Oncogene
27
4877-4887
2008
Homo sapiens
brenda
Iglesias-Baena, I.; Barranco-Medina, S.; Lazaro-Payo, A.; Lopez-Jaramillo, F.J.; Sevilla, F.; Lazaro, J.J.
Characterization of plant sulfiredoxin and role of sulphinic form of 2-Cys peroxiredoxin
J. Exp. Bot.
61
1509-1521
2010
Arabidopsis thaliana, Arabidopsis thaliana Columbia
brenda
Moon, J.C.; Kim, G.M.; Kim, E.K.; Lee, H.N.; Ha, B.; Lee, S.Y.; Jang, H.H.
Reversal of 2-Cys peroxiredoxin oligomerization by sulfiredoxin
Biochem. Biophys. Res. Commun.
432
291-295
2013
Saccharomyces cerevisiae
brenda
Roussel, X.; Boukhenouna, S.; Rahuel-Clermont, S.; Branlant, G.
The rate-limiting step of sulfiredoxin is associated with the transfer of the gamma-phosphate of ATP to the sulfinic acid of overoxidized typical 2-Cys peroxiredoxins
FEBS Lett.
585
574-578
2011
Saccharomyces cerevisiae
brenda
Chi, Y.H.; Kim, S.Y.; Jung, I.J.; Shin, M.R.; Jung, Y.J.; Park, J.H.; Lee, E.S.; Maibam, P.; Kim, K.S.; Park, J.H.; Kim, M.J.; Hwang, G.Y.; Lee, S.Y.
Dual functions of Arabidopsis sulfiredoxin: acting as a redox-dependent sulfinic acid reductase and as a redox-independent nuclease enzyme
FEBS Lett.
586
3493-3499
2012
Arabidopsis thaliana
brenda
Baek, J.Y.; Han, S.H.; Sung, S.H.; Lee, H.E.; Kim, Y.M.; Noh, Y.H.; Bae, S.H.; Rhee, S.G.; Chang, T.S.
Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2
J. Biol. Chem.
287
81-89
2012
Mus musculus (Q9D975), Mus musculus
brenda
Iglesias-Baena, I.; Barranco-Medina, S.; Sevilla, F.; Lazaro, J.J.
The dual-targeted plant sulfiredoxin retroreduces the sulfinic form of atypical mitochondrial peroxiredoxin
Plant Physiol.
155
944-955
2011
Pisum sativum (D2KKL9), Pisum sativum, Arabidopsis thaliana (Q8GY89)
brenda
Shi, S.; Guo, Y.; Lou, Y.; Li, Q.; Cai, X.; Zhong, X.; Li, H.
Sulfiredoxin involved in the protection of peroxiredoxins against hyperoxidation in the early hyperglycaemia
Exp. Cell Res.
352
273-280
2017
Rattus norvegicus
brenda
Rhee, S.G.; Kil, I.S.
Mitochondrial H2O2 signaling is controlled by the concerted action of peroxiredoxin III and sulfiredoxin Linking mitochondrial function to circadian rhythm
Free Radic. Biol. Med.
99
120-127
2016
Mus musculus
brenda
Calderon, A.; Lazaro-Payo, A.; Iglesias-Baena, I.; Camejo, D.; Lazaro, J.J.; Sevilla, F.; Jimenez, A.
Glutathionylation of pea chloroplast 2-Cys Prx and mitochondrial Prx IIF affects their structure and peroxidase activity and sulfiredoxin deglutathionylates only the 2-Cys Prx
Front. Plant Sci.
8
118
2017
Pisum sativum
brenda
Sevilla, F.; Camejo, D.; Ortiz-Espin, A.; Calderon, A.; Lazaro, J.J.; Jimenez, A.
The thioredoxin/peroxiredoxin/sulfiredoxin system current overview on its redox function in plants and regulation by reactive oxygen and nitrogen species
J. Exp. Bot.
66
2945-2955
2015
Arabidopsis thaliana
brenda
Li, Q.; Yu, S.; Wu, J.; Zou, Y.; Zhao, Y.
Sulfiredoxin-1 protects PC12 cells against oxidative stress induced by hydrogen peroxide
J. Neurosci. Res.
91
861-870
2013
Rattus norvegicus
brenda
Kil, I.S.; Bae, S.H.; Rhee, S.G.
Study of the signaling function of sulfiredoxin and peroxiredoxin III in isolated adrenal gland unsuitability of clonal and primary adrenocortical cells
Methods Enzymol.
527
169-181
2013
Mus musculus
brenda
Forshaw, T.E.; Reisz, J.A.; Nelson, K.J.; Gumpena, R.; Lawson, J.R.; Joensson, T.J.; Wu, H.; Clodfelter, J.E.; Johnson, L.C.; Furdui, C.M.; Lowther, W.T.
Specificity of human sulfiredoxin for reductant and peroxiredoxin oligomeric state
Antioxidants (Basel)
10
946
2021
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Liu, M.; Wang, J.; Li, X.; Sylvanno, M.J.; Li, M.; Zhang, M.; Wang, M.
The crystal structure of sulfiredoxin from Arabidopsis thaliana revealed a more robust antioxidant mechanism in plants
Biochem. Biophys. Res. Commun.
520
347-352
2019
Arabidopsis thaliana (Q8GY89), Arabidopsis thaliana
brenda
Chawsheen, H.A.; Jiang, H.; Ying, Q.; Ding, N.; Thapa, P.; Wei, Q.
The redox regulator sulfiredoxin forms a complex with thioredoxin domain-containing 5 protein in response to ER stress in lung cancer cells
J. Biol. Chem.
294
8991-9006
2019
Homo sapiens (Q9BYN0), Homo sapiens
brenda
Kim, M.; Kwon, J.; Goo, J.I.; Choi, Y.; Cho, A.E.
Elucidation of the inhibition mechanism of sulfiredoxin using molecular modeling and development of its inhibitors
J. Mol. Graph. Model.
92
208-215
2019
Homo sapiens (Q9BYN0)
brenda
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