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Information on EC 1.11.1.28 - lipoyl-dependent peroxiredoxin and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WQB7

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     1 Oxidoreductases
         1.11 Acting on a peroxide as acceptor
             1.11.1 Peroxidases
                1.11.1.28 lipoyl-dependent 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 {single/111115a::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 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. The 1-Cys Prxs conserve only the peroxidatic cysteine, so its regeneration involves direct interaction with a reductant molecule. Two types of lipoyl-dependent peroxiredoxins have been reported from bacteria. One type is the AhpC/AhpD system, originally described from Mycobacterium tuberculosis. In that system, AhpC catalyses reduction of the substrate, resulting in an intramolecular disulfide. AhpD then forms an intermolecular disulfide crosslink with AhpC, reducing it back to active state. AhpD is reduced in turn by lipoylated proteins. The second type, which has been characterized in Xylella fastidiosa, consists of only one type of subunit, which interacts directly with lipoylated proteins.
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Mycobacterium tuberculosis
UNIPROT: P9WQB7
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The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
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a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine
+
ROOH
=
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine
+
H2O
+
ROH
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine
+
=
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine
+
+
Synonyms
organic hydroperoxide resistance, organic hydroperoxide resistance protein, peroxiredoxin ahpc, ahpcd, mfohr, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
AhpC
-
-
-
-
Ohr
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
lipoyl: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 [2]. 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 {single/111115a::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 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. The 1-Cys Prxs conserve only the peroxidatic cysteine, so its regeneration involves direct interaction with a reductant molecule. Two types of lipoyl-dependent peroxiredoxins have been reported from bacteria. One type is the AhpC/AhpD system, originally described from Mycobacterium tuberculosis. In that system, AhpC catalyses reduction of the substrate, resulting in an intramolecular disulfide. AhpD then forms an intermolecular disulfide crosslink with AhpC, reducing it back to active state. AhpD is reduced in turn by lipoylated proteins. The second type, which has been characterized in Xylella fastidiosa, consists of only one type of subunit, which interacts directly with lipoylated proteins.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + 7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + 7alpha-hydroxy-3beta-hydroxycholest-6-ene
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + cumene hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + cumene hydroxide
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + H2O2
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + 2 H2O
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + oleic acid hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + oleic acid
show the reaction diagram
poor substrate
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + tert-butyl hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + tert-butyl alcohol
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + trans-pinocarveylhydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + trans-pinocarveyl alcohol
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + 7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + 7alpha-hydroxy-3beta-hydroxycholest-6-ene
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + cholesterol hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + cholesterol hydroxide
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + cumene hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + cumene hydroxide
show the reaction diagram
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + H2O2
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + 2 H2O
show the reaction diagram
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + oleic acid hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + oleic acid
show the reaction diagram
poor substrate
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + tert-butyl hydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + tert-butyl alcohol
show the reaction diagram
-
-
-
?
a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + trans-pinocarveylhydroperoxide
a [lipoyl-carrier protein]-N6-lipoyl-L-lysine + H2O + trans-pinocarveyl alcohol
show the reaction diagram
-
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.091
7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
pH 7.0, 25°C
0.55
cumene hydroperoxide
pH 7.0, 25°C
1.1
tert-butyl hydroperoxide
pH 7.0, 25°C
0.86
trans-pinocarveylhydroperoxide
pH 7.0, 25°C
0.132
7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
pH 7.0, 25°C
0.052
cumene hydroperoxide
pH 7.0, 25°C
0.23
tert-butyl hydroperoxide
pH 7.0, 25°C
0.15
trans-pinocarveylhydroperoxide
pH 7.0, 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.147
7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
pH 7.0, 25°C
0.033
cumene hydroperoxide
pH 7.0, 25°C
0.088
H2O2
pH 7.0, 25°C
0.035
tert-butyl hydroperoxide
pH 7.0, 25°C
0.015
trans-pinocarveylhydroperoxide
pH 7.0, 25°C
0.178
7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
pH 7.0, 25°C
0.067
cumene hydroperoxide
pH 7.0, 25°C
0.085
H2O2
pH 7.0, 25°C
0.06
tert-butyl hydroperoxide
pH 7.0, 25°C
0.013
trans-pinocarveylhydroperoxide
pH 7.0, 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.62
7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
pH 7.0, 25°C
0.06
cumene hydroperoxide
pH 7.0, 25°C
0.059
H2O2
pH 7.0, 25°C
0.032
tert-butyl hydroperoxide
pH 7.0, 25°C
0.017
trans-pinocarveylhydroperoxide
pH 7.0, 25°C
1.35
7alpha-hydroperoxy-3beta-hydroxycholest-6-ene
pH 7.0, 25°C
1.2
cumene hydroperoxide
pH 7.0, 25°C
0.056
H2O2
pH 7.0, 25°C
0.26
tert-butyl hydroperoxide
pH 7.0, 25°C
0.087
trans-pinocarveylhydroperoxide
pH 7.0, 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
mutant enzymes H137F and H132F
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
physiological function
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, crystal structures of the H137F and H132Q mutants
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C174S
mutant enzyme retains about 10% of the wild-type activity
C176S
mutant enzyme retains about 10% of the wild-type activity
C61S
inactive mutant enzyme
C130S
expressed in yield comparable to that of the wild-type protein. Mutation decreases activity to less than 5% of the wild-type enzyme
C133S
expressed in yield comparable to that of the wild-type protein. Mutation completely suppresses the activity
Cys129
mutant enzyme shows no activity with cumene hydroperoxide
Cys132
mutant enzyme retains about 5% of the wild-type activity with cumene hydroperoxide
E118F
expressed at 20% of the wild-type expression level. Mutation decreases catalytic activity
E118Q
expressed at 20% of the wild-type expression level. Mutation modestly loweres the catalytic activity
H132F
expressed in yield comparable to that of the wild-type protein. Mutation decreases the catalytic activity
H132Q
mutant tends to unfold and degrade relatively easily. Mutation decreases the catalytic activity. The H137Q mutation decreases the activity more severely than the H132Q mutation
H137F
expressed in yield comparable to that of the wild-type protein. Mutation decreases the catalytic activity
H137Q
expressed at 20% of the wild-type expression level. Mutation decreases the catalytic activity. The H137Q mutation decreases the activity more severely than the H132Q mutation
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
AhpCis a critical element of the antioxidant defense system of Mycobacterium tuberculosis and may be suitable target for the development of novel anti-tuberculosis strategies
medicine
AhpD is a critical element of the antioxidant defense system of Mycobacterium tuberculosis and may be suitable target for the development of novel anti-tuberculosis strategies
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shi, S.; Ehrt, S.
Dihydrolipoamide acyltransferase is critical for Mycobacterium tuberculosis pathogenesis
Infect. Immun.
74
56-63
2006
Mycobacterium tuberculosis (P9WQB5), Mycobacterium tuberculosis (P9WQB7), Mycobacterium tuberculosis ATCC 25618 (P9WQB5), Mycobacterium tuberculosis ATCC 25618 (P9WQB7)
Manually annotated by BRENDA team
Hillas, P.J.; del Alba, F.S.; Oyarzabal, J.; Wilks, A.; Ortiz De Montellano, P.R.
The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis
J. Biol. Chem.
275
18801-18809
2000
Mycobacterium tuberculosis (P9WQB5), Mycobacterium tuberculosis (P9WQB7), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25618 (P9WQB5), Mycobacterium tuberculosis ATCC 25618 (P9WQB7)
Manually annotated by BRENDA team
Koshkin, A.; Nunn, C.M.; Djordjevic, S.; Ortiz de Montellano, P.R.
The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics
J. Biol. Chem.
278
29502-29508
2003
Mycobacterium tuberculosis (P9WQB5), Mycobacterium tuberculosis ATCC 25618 (P9WQB5)
Manually annotated by BRENDA team