show all | hide all No of entries

Information on EC 1.11.1.15 - peroxiredoxin and Organism(s) Rattus norvegicus and UniProt Accession Q9Z0V5

for references in articles please use BRENDA:EC1.11.1.15
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
     1 Oxidoreductases
         1.11 Acting on a peroxide as acceptor
             1.11.1 Peroxidases
                1.11.1.15 peroxiredoxin
IUBMB Comments
Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins . The peroxidase reaction comprises two steps centred around a redox-active cysteine called the peroxidatic cysteine. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid) (see mechanism). The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the 'resolving' cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants (R'-SH) (e.g. thioredoxin, AhpF, tryparedoxin or AhpD), completing the catalytic cycle. In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond . To recycle the disulfide, known atypical 2-Cys Prxs appear to use thioredoxin as an electron donor . The 1-Cys Prxs conserve only the peroxidatic cysteine, so that its oxidized form is directly reduced to cysteine by the reductant molecule .
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Rattus norvegicus
UNIPROT: Q9Z0V5
Word Map
The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota
The taxonomic range for the selected organisms is: Rattus norvegicus
Reaction Schemes
Synonyms
1-Cys peroxiredoxin, 1-Cys Prdx, 1-Cys Prx, 1-Cys type Prx, 1Cys-peroxiredoxin, 2-CP, 2-Cys peroxiredoxin, 2-Cys peroxiredoxin 4, 2-Cys peroxiredoxin TPx-1, 2-Cys Prx, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1-Cys Prdx
248
-
2-Cys peroxiredoxin
248
-
HBP23/Prx I
248
-
heme-binding protein 23/peroxiredoxin
248
belongs to the 2-Cys peroxiredoxin type I family and exhibits peroxidase activity coupled with reduced thioredoxin as an electron donor
peroxiredoxin 6
peroxiredoxin IV
248
-
peroxiredoxin-4
299303
-
Prdx6
Prx I
Prx II
Prx III
283477
-
PRx IV
Prx V
Prx VI
Prx-4
299303
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
thiol-containing-reductant:hydroperoxide oxidoreductase
Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins [1]. The peroxidase reaction comprises two steps centred around a redox-active cysteine called the peroxidatic cysteine. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid) (see mechanism). The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the 'resolving' cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants (R'-SH) (e.g. thioredoxin, AhpF, tryparedoxin or AhpD), completing the catalytic cycle. In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond [1]. To recycle the disulfide, known atypical 2-Cys Prxs appear to use thioredoxin as an electron donor [3]. The 1-Cys Prxs conserve only the peroxidatic cysteine, so that its oxidized form is directly reduced to cysteine by the reductant molecule [4].
CAS REGISTRY NUMBER
COMMENTARY hide
207137-51-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine hydroperoxide + GSH
?
show the reaction diagram
-
specific substrate for peroxiredoxin 6
-
-
?
2 GSH + ROOH
GSSG + H2O + ROH
show the reaction diagram
H2O2 + 2 GSH
2 H2O + GSSG
show the reaction diagram
-
-
-
-
?
H2O2 + GSH
H2O + GSSG
show the reaction diagram
H2O2 + reduced thioredoxin
H2O + oxidized thioredoxin
show the reaction diagram
tert-butyl hydroperoxide + reduced dithiothreitol
tert-butanol + oxidized dithiothreitol
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 GSH + ROOH
GSSG + H2O + ROH
show the reaction diagram
-
glutathione is the primary native reductant
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Mercaptosuccinate
-
a thiol-active agent that inhibits the peroxidase activity of Prdx6 while the PLA2 activity is unaffected
MJ33
-
a phospholipid substrate intermediate analogue, inhibits the PLA2 activity of Prdx6 but has no effect on peroxidase activity
additional information
-
serine protease inhibitors inhibit the PLA2 activity of Prdx6 but have no effect on peroxidase activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.03
-
mutant enzyme C83S/R128E, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C; mutant enzyme C83S/R128E, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C
0.04
-
mutant enzyme C83S/R128A, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C; mutant enzyme C83S/R128A, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C; mutant enzyme C83S/R128K, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
0.08
-
mutant enzyme C83S/R128K, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C
0.1
-
mutant enzyme C83S/R151A, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C; mutant enzyme C83S/R151E, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
0.12
-
mutant enzyme C83S/R151A, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C; mutant enzyme C83S/R151K, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
0.18
-
mutant enzyme C83S/R151E, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C
0.19
-
mutant enzyme C83S/R151K, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C
0.28
-
mutant enzyme H26A, using 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine hydroperoxide as substrate, at pH 7.4
0.9
-
wild type enzyme, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
1
-
mutant enzyme C173S, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
1.07
-
mutant enzyme C83S, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
1.95
-
mutant enzyme C83S/C173S, using dithiothreitol as a substrate, in 50 mM HEPES-NaOH (pH 7.0), at 25°C
2.32
-
mutant enzyme C83S, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C
2.74
-
wild type enzyme, using thioredoxin as a substrate, in 150 mM potassium phosphate buffer, pH 7.4, at 25°C
5.25
-
mutant enzyme D140A, using 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine hydroperoxide as substrate, at pH 7.4
5.6
-
mutant enzyme H26A, using H2O2 as substrate, at pH 7.4
5.72
-
mutant enzyme S32A, using H2O2 as substrate, at pH 7.4
6
-
wild type enzyme, using 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine hydroperoxide as substrate, at pH 7.4
6.15
-
mutant enzyme D140A, using H2O2 as substrate, at pH 7.4
6.2
-
wild type enzyme, using H2O2 as substrate, at pH 7.4
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.34
isoelectric focusing
5.64
isoelectric focusing
6.18
isoelectric focusing
7.14
isoelectric focusing
8.27
isoelectric focusing
8.94
isoelectric focusing
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
less than 0.002 mg Prx I per mg of soluble protein Prx I, 0.002 mg Prx II per mg of soluble protein, less than 0.004 mg Prx III per mg of soluble protein, 0.0003 mg Prx V per mg of soluble protein and 0.0003 mg Prx VI per mg of soluble protein
Manually annotated by BRENDA team
-
0.0013 mg Prx I per mg of soluble protein Prx I, 0.0013 mg Prx II per mg of soluble protein, 0.0005 mg Prx III per mg of soluble protein, 0.0007 mg Prx V per mg of soluble protein and 0.0007 mg Prx VI per mg of soluble protein
Manually annotated by BRENDA team
-
0.002 mg Prx I per mg of soluble protein Prx I, 0.0033 mg Prx II per mg of soluble protein, 0.0007 mg Prx III per mg of soluble protein, 0.0002 mg Prx V per mg of soluble protein and 0.0002 mg Prx VI per mg of soluble protein
Manually annotated by BRENDA team
-
0.0002 mg Prx I per mg of soluble protein Prx I, 0.0007 mg Prx II per mg of soluble protein, less than 0.0003 mg Prx III per mg of soluble protein, 0.0007 mg Prx V per mg of soluble protein and 0.0002 mg Prx VI per mg of soluble protein
Manually annotated by BRENDA team
-
0.0003 mg Prx I per mg of soluble protein Prx I, 0.0007 mg Prx II per mg of soluble protein, 0.0003 mg Prx III per mg of soluble protein, 0.0003 mg Prx V per mg of soluble protein and 0.00003 mg Prx VI per mg of soluble protein
Manually annotated by BRENDA team
-
0.0007 mg Prx I per mg of soluble protein Prx I, 0.0007 mg Prx II per mg of soluble protein, 0.0005 mg Prx III per mg of soluble protein, 0.0003 mg Prx V per mg of soluble protein and 0.0002 mg Prx VI per mg of soluble protein
Manually annotated by BRENDA team
additional information
-
within organs, expression of Prdx is greatest in epithelium such as apical regions of respiratory epithelium and skin epidermis, tissue distribution, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
treatment of A-549 cells with peroxides leads to translocation of Prdx6 from the cytosol to the cell membrane
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis
additional information
-
regulation of Prdx6 gene regulation, overview. Transcription is activated by binding of the transcription factor Nrf2 to the ARE whereas transcription is inhibited by the binding of Nrf3. Prdx6 expression also is responsive to hormonal regulation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
PRDX4_RAT
273
0
31007
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22000
23000
-
10 * 23000, SDS-PAGE, the wild type enzyme exists as a mixture of various forms, favoring the homodecamer at higher protein concentration and lower ionic salt concentration and in the presence of dithiothreitol
27000
-
x * 27000, SDS-PAGE
44000
-
dimer, SDS-PAGE
230000
-
decamer, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 27000, SDS-PAGE
dimer
-
2 * 22000, SDS-PAGE, the protein readily interconverts between dimer and oligomeric forms
homodecamer
-
10 * 23000, SDS-PAGE, the wild type enzyme exists as a mixture of various forms, favoring the homodecamer at higher protein concentration and lower ionic salt concentration and in the presence of dithiothreitol
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
MAP kinase mediated phosphorylation of Prdx6 at residue T177, results in increased phospholipase A2 activity, but phosphorylation has no effect on the peroxidase activity of Prdx6
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C126S
very weak activity both with substrate H2O2 and t-butyl hydroperoxide
C150S
activity similar to wild-type
C247S
weak activity both with substrate H2O2 and t-butyl hydroperoxide
C173S
-
decameric mutant enzyme, cannot form an intermolecular disulfide bridge in the vicinity of the active site under oxidative conditions
C47S
-
inactive
C52S
-
decameric mutant enzyme, inactive, cannot form an intermolecular disulfide bridge in the vicinity of the active site under oxidative conditions
C83S
-
dimeric mutant enzyme, mutant exhibits similar peroxidase activity compared to the wild type enzyme
C83S/C173S
-
increased specific activity with dithiothreitol compared to the wild type enzyme, shows no activity with thioredoxin
C83S/R128A
-
reduced specific activity compared to the wild type enzyme
C83S/R128E
-
reduced specific activity compared to the wild type enzyme
C83S/R128K
-
reduced specific activity compared to the wild type enzyme
C83S/R151A
-
reduced specific activity compared to the wild type enzyme
C83S/R151EA
-
reduced specific activity compared to the wild type enzyme
C83S/R151K
-
reduced specific activity compared to the wild type enzyme
D140A
-
mutant shows decreased peroxidase activity
H26A
-
mutant shows decreased peroxidase activity
S32A
-
mutant shows decreased peroxidase activity with H2O2 and no activity with 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine hydroperoxide as substrate
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PRX6 is resistant to inactivation via aldehyde modification
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
column chromatography and YMC-10 gel filtration
-
DE-52 column chromatography and 2',5'-ADP-Sepharose affinity column chromatography
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination, analysis, and comparison
-
expressed in Escherichia coli cells; expression in A-549 cells
-
expressed in Escherichia coli strain JM109
-
expression in COS cells and in Sf21 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transcription of Prdx6 message in dermal epithelium is induced by treatment with keratinocyte growth factor, a response of presumed importance related to wound healing, requiring ARE and Nrf2. Dexamethasone induces Prdx6 expression in adult lung cells and regulates transcription through its interaction with a glucocorticoid response element in the promoter region of the Prdx6 gene. Oxidant stress is, e.g. by H2O2, paraquat, a potent inducer of Prdx6 expression and stimulates Prdx6 gene expression by a transcriptional mechanism involving its antioxidant response element, ARE
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rhee, S.G.; Kang, S.W.; Chang, T.S.; Jeong, W.; Kim, K.
Peroxiredoxin, a novel family of peroxidases
IUBMB Life
52
35-41
2001
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Okado-Matsumoto, A.; Matsumoto, A.; Fujii, J.; Taniguchi, N.
Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions
J. Biochem.
127
493-501
2000
Rattus norvegicus
Manually annotated by BRENDA team
Manevich, Y.; Fisher, A.B.
Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism
Free Radic. Biol. Med.
38
1422-1432
2005
Bos taurus (O77834), Homo sapiens (P30041), Mus musculus, Mus musculus (O08709), Rattus norvegicus (O35244), Sus scrofa (Q9TSX9)
Manually annotated by BRENDA team
Lee, C.K.; Kim, H.J.; Lee, Y.R.; So, H.H.; Park, H.J.; Won, K.J.; Park, T.; Lee, K.Y.; Lee, H.M.; Kim, B.
Analysis of peroxiredoxin decreasing oxidative stress in hypertensive aortic smooth muscle
Biochim. Biophys. Acta
1774
848-855
2007
Rattus norvegicus (O35244), Rattus norvegicus (P35704), Rattus norvegicus (Q63716), Rattus norvegicus (Q9R063), Rattus norvegicus (Q9Z0V6)
Manually annotated by BRENDA team
Matsumura, T.; Okamoto, K.; Iwahara, S.; Hori, H.; Takahashi, Y.; Nishino, T.; Abe, Y.
Dimer-oligomer interconversion of wild-type and mutant rat 2-Cys peroxiredoxin: disulfide formation at dimer-dimer interfaces is not essential for decamerization
J. Biol. Chem.
283
284-293
2008
Rattus norvegicus (Q63716)
Manually annotated by BRENDA team
Manevich, Y.; Shuvaeva, T.; Dodia, C.; Kazi, A.; Feinstein, S.I.; Fisher, A.B.
Binding of peroxiredoxin 6 to substrate determines differential phospholipid hydroperoxide peroxidase and phospholipase A(2) activities
Arch. Biochem. Biophys.
485
139-149
2009
Rattus norvegicus (O35244)
Manually annotated by BRENDA team
Roede, J.R.; Carbone, D.L.; Doorn, J.A.; Kirichenko, O.V.; Reigan, P.; Petersen, D.R.
In vitro and in silico characterization of peroxiredoxin 6 modified by 4-hydroxynonenal and 4-oxononenal
Chem. Res. Toxicol.
21
2289-2299
2008
Rattus norvegicus
Manually annotated by BRENDA team
Fisher, A.B.
Peroxiredoxin 6: A bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities
Antioxid. Redox Signal.
15
831-844
2010
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Ikeda, Y.; Nakano, M.; Ihara, H.; Ito, R.; Taniguchi, N.; Fujii, J.
Different consequences of reactions with hydrogen peroxide and t-butyl hydroperoxide in the hyperoxidative inactivation of rat peroxiredoxin-4
J. Biochem.
149
443-453
2011
Rattus norvegicus (Q9Z0V5)
Manually annotated by BRENDA team
Select items on the left to see more content.