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Information on EC 7.1.1.1 - proton-translocating NAD(P)+ transhydrogenase
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7.1.1.1 proton-translocating NAD(P)+ transhydrogenaseIUBMB Comments
The enzyme is a membrane bound proton-translocating pyridine nucleotide transhydrogenase that couples the reversible reduction of NADP by NADH to an inward proton translocation across the membrane. In the bacterium Escherichia coli the enzyme provides a major source of cytosolic NADPH. Detoxification of reactive oxygen species in mitochondria by glutathione peroxidases depends on NADPH produced by this enzyme.
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Word Map
- 7.1.1.1
- nadp+
-
nadph-binding
- 3-acetylpyridine-nad+
- thio-nadp+
-
proteoliposomes
-
hydride
-
cysteine-free
-
membrane-spanning
-
dissipation
-
protrude
-
alpha-helices
-
detergent-dispersed
-
microbalance
- quartz
-
unspecific
-
palmitoyl-coenzyme
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
proton-pumping nicotinamide nucleotide transhydrogenase, proton translocating nicotinamide nucleotide transhydrogenase, proton-translocating nad(p)+ transhydrogenase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 1.6.1.5
-
-
formerly
-
nicotinamide nucleotide transhydrogenase
NNT
pntA
pntB
proton-translocating NAD(P)(+) transhydrogenase
proton-translocating nicotinamide nucleotide transhydrogenase
-
-
proton-translocating transhydrogenase
pyridine nucleotide transhydrogenase
transhydrogenase
TT_C1779
NNT
-
-
-
-
pntA
-
-
-
-
pntB
-
-
-
-
proton-translocating transhydrogenase
-
-
proton-translocating transhydrogenase
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NADPH + NAD+ + H+[side 1] = NADP+ + NADH + H+[side 2]
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
-
,
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SYSTEMATIC NAME
IUBMB Comments
NADPH:NAD+ oxidoreductase (H+-transporting)
The enzyme is a membrane bound proton-translocating pyridine nucleotide transhydrogenase that couples the reversible reduction of NADP by NADH to an inward proton translocation across the membrane. In the bacterium Escherichia coli the enzyme provides a major source of cytosolic NADPH. Detoxification of reactive oxygen species in mitochondria by glutathione peroxidases depends on NADPH produced by this enzyme.
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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
1,N6-etheno-NADPH + NAD+ + H+[side 1]
1,N6-etheno-NADP+ + NADH + H+[side 2]
-
-
-
-
r
1,N6-etheno-NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
1,N6-etheno-NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
deamino-NADPH + NAD+ + H+[side 1]
deamino-NADP+ + NADH + H+[side 2]
-
-
-
-
r
deamino-NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
deamino-NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
NADPH + 3-acetylpyridine-NAD+ + H+[side 1]
NADP+ + 3-acetylpyridine-NADH + H+[side 2]
-
-
-
-
?
NADPH + oxidized 3-acetylpyridin-adenine dinucleotide + H+[side 1]
NADP+ + reduced 3-acetylpyridin-adenine dinucleotide + H+[side 2]
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
-
?
NADPH + oxidized 3-acetylpyridine adenine dinucleotide + H+ [side 1]
NADP+ + reduced 3-acetylpyridine adenine dinucleotide + H+[side 2]
-
-
-
-
?
NADPH + oxidized 3-acetylpyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced 3-acetylpyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+/in
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+/out
-
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
NADPH + oxidized acetylpyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetylpyridine adenine dinucleotide + H+[side 2]
-
-
-
-
?
additional information
?
-
-
NADP(H) binding leads to perturbation of a deeply buried part of the polypeptide backbone and to protonation of a carboxylic acid residue
-
-
?
H+(in) + NAD+ + NADPH
H+(out) + NADH + NADP+
-
-
-
?
H+/out + NADH + NADP+
H+/in + NAD+ + NADPH
the enzyme couples the redox reaction between NAD(H) and NADP(H) to the inward transport of protons across a membrane
-
-
?
H+/out + NADH + NADP+
H+/in + NAD+ + NADPH
-
the enzyme couples the redox reaction between NAD(H) and NADP(H) to the transport of protons across a membrane
-
-
?
NADH + NADP+
NAD+ + NADPH
-
-
-
-
r
NADH + NADP+
NAD+ + NADPH
-
reaction is catalyzed by a mixture of recombinant domains dI and dIII of either species or by a hybrid mixture of domains I and III from both species
-
-
?
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the outside in translocation of protons across membrane
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, cellular regeneration of NADPH
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, major source of NADPH
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and reduction of glutathione
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for the reduction of glutathione, reverse reaction results in outward proton translocation and creation of a proton motive force
-
-
r
NADH + NADP+
NAD+ + NADPH
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and glutathione reduction
-
-
r
NADH + NADP+
NAD+ + NADPH
-
solubilized and purified enzyme does not catalyze reduction of acetyl pyridine adenine dinucleotide by NADH in absence of NADP+
-
-
?
NADH + NADP+
NAD+ + NADPH
-
reaction is catalyzed by a mixture of recombinant domains dI and dIII of either species or by a hybrid mixture of domains I and III from both species
-
-
?
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the outside in translocation of protons across membrane, provides NADPH for biosynthesis and reduction of glutathione, reaction is stereospecific between th 4A position of NAD(H) to the 4B position of NADP(H)
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane
-
-
r
NADH + NADP+
NAD+ + NADPH
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and glutathione reduction
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and reduction of glutathione
-
-
r
NADP+ + NADH
NADPH + NAD+
-
mitochondrial transhydrogenase is stereospecific for the 4A-NADH and 4B-NADPH hydrogens
-
-
?
NADP+ + NADH
NADPH + NAD+
-
mitochondrial transhydrogenase is stereospecific for the 4A-NADH and 4B-NADPH hydrogens
-
-
?
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
?
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
r
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
?
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
r
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039
-
-
-
?
NADPH + oxidized 3-acetylpyridin-adenine dinucleotide + H+[side 1]
NADP+ + reduced 3-acetylpyridin-adenine dinucleotide + H+[side 2]
-
-
-
-
?
NADPH + oxidized 3-acetylpyridin-adenine dinucleotide + H+[side 1]
NADP+ + reduced 3-acetylpyridin-adenine dinucleotide + H+[side 2]
-
-
-
-
?
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
?
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
?
NADPH + oxidized acetyl pyridine adenine dinucleotide + H+[side 1]
NADP+ + reduced acetyl pyridine adenine dinucleotide + H+[side 2]
-
-
-
-
r
thio-NADPH + NAD+ + H+[side 1]
thio-NADP+ + NADH + H+[side 2]
-
-
-
-
?
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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
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
-
?
H+/out + NADH + NADP+
H+/in + NAD+ + NADPH
the enzyme couples the redox reaction between NAD(H) and NADP(H) to the inward transport of protons across a membrane
-
-
?
H+/out + NADH + NADP+
H+/in + NAD+ + NADPH
-
the enzyme couples the redox reaction between NAD(H) and NADP(H) to the transport of protons across a membrane
-
-
?
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the outside in translocation of protons across membrane
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, cellular regeneration of NADPH
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, major source of NADPH
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and reduction of glutathione
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for the reduction of glutathione, reverse reaction results in outward proton translocation and creation of a proton motive force
-
-
r
NADH + NADP+
NAD+ + NADPH
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and glutathione reduction
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the outside in translocation of protons across membrane, provides NADPH for biosynthesis and reduction of glutathione, reaction is stereospecific between th 4A position of NAD(H) to the 4B position of NADP(H)
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane
-
-
r
NADH + NADP+
NAD+ + NADPH
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and glutathione reduction
-
-
r
NADH + NADP+
NAD+ + NADPH
-
links hydride transfer between NAD(H) and NADP(H) to the translocation of protons across membrane, provides NADPH for biosynthesis and reduction of glutathione
-
-
r
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
?
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
r
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
?
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
-
-
-
-
r
NADPH + NAD+ + H+[side 1]
NADP+ + NADH + H+[side 2]
Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039
-
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
no flavin cofactor, differentiation from EC 1.6.1.1.
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
K+
Mg2+
Na+
-
strong activation of forward reaction, i.e. the reduction of NADP+ by NADH, in the light at concentrations of approx. 50-80 mM, half-maximal activation at 10 mM
Ca2+
-
strong activation of forward reaction in the light at concentrations above 0.1 mM
K+
-
strong activation of forward reaction, i.e. the reduction of NADP+ by NADH, in the light at concentrations of approx. 50-80 mM, half-maximal activation at 10 mM
Mg2+
-
strong activation of forward reaction, i.e. the reduction of NADP+ by NADH, in the light at concentrations above 0.1 mM
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(4-maleimidoanilino)-naphthalene-6-sulfonic acid
-
0.004 mM, 2 h incubation, 75% inhibition of reverse reaction catalyzed by A348C mutant enzyme, 95% inhibition of A390C mutant enzyme after 1 h, 90% inhibition of K424C mutant enzyme after 1 h, 55% inhibition of R425C mutant enzyme after 1h
Butane-2,3-dione
-
40 mM, almost complete inactivation of enzyme activity in chromatophores after 12 min, NAD+ and NADP+ partially protect, complete protection by a combination of NAD+ and NADP+
Cd2+
-
low concentrations of Cd2+ strongly inhibit revers transhydrogenation
N,N'-Dicylclohexylcarbodiimide
-
NADH protects from inhibition, NADP+ and to a lesser extent NADPH increase the rate of inhibition
N-cyclohexyl-N'-(4-dimethylaminonaphthyl)carbodiimide
-
about 25% residual activity after 200 min at 0.5 mM
NADP+
-
mixed product inhibition vs. acetylpyridine adenine dinucleotide, competitive vs. NADPH
oxidized 3-acetylpyridin-adenine dinucleotide
-
high concentrations of oxidized 3-acetylpyridin-adenine dinucleotide lead to substrate inhibition
reduced acetylpyridine adenine dinucleotide
-
competitive inhibition vs. oxidized acetylpyridine adenine dinucleotide, mixed inhibition vs. NADPH
Zn2+
-
low concentrations of Zn2+ strongly inhibit revers transhydrogenation
N,N'-dicyclohexylcarbodiimide
-
NADH protects the enzyme against inhibition by N,N'-dicyclohexylcarbodiimide, while NADP+ , and to a lesser extent NADPH increase the rate of inhibition
N,N'-dicyclohexylcarbodiimide
-
about 12% residual activity after 180 min at 0.5 mM
N,N'-dicyclohexylcarbodiimide
-
modification of the enzyme with N,N'-dicyclohexylcarbodiimide leads to inhibition of the rate of release of NADP+ and NADPH from the enzyme, but has a much smaller effect on the binding and release of NAD+, NADH and their analogues and on the interconversion of the ternary complexes of the enzyme with its substrates
N-ethylmaleimide
-
0.2 mM, 57% inhibition of reverse reaction in A348C mutant enzyme, 60% inhibition of K424C mutant enzyme, more than 95% inhibition of A390C mutant enzyme after 1h, R425C mutant enzyme is not inhibited
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
carbonylcyanide-4-trifluoromethoxyphenyl hydrazone
-
0.002 mM stimulates the rate of the forward reaction by 8fold and of the reverse reaction by 10fold
light
-
forward reaction in chromatophores is accelerated more than 20fold during illumination with photosynthetically active light
-
phosphatidylcholine
presence of phospholipid is required, most effective phopholipid tested
additional information
presence of phospholipid is required, without phospholipid activity is rapidly lost
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0667
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of wild-type domain III/R. rubrum domain I mixture
0.1
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of A432C mutant domain III/R. rubrum domain I mixture
0.117
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of D393C mutant domain III/R. rubrum domain I mixture
0.167
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of H345C mutant domain III/R. rubrum domain I mixture
0.167
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of R350C mutant domain III/R. rubrum domain I mixture
0.283
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of K424C mutant domain III/R. rubrum domain I mixture
0.283
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of R425C mutant domain III/R. rubrum domain I mixture
0.55
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of A348C mutant domain III/R. rubrum domain I mixture
0.567
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of G430C mutant domain III/R. rubrum domain I mixture
0.917
reduced acetylpyridine adenine dinucleotide
-
reverse reaction of D392C mutant domain III/R. rubrum domain I mixture
10
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of R425C mutant domain III/R. rubrum domain I mixture
11.7
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of G430C mutant domain III/R. rubrum domain I mixture
15
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of D392C mutant domain III/R. rubrum domain I mixture
20.8
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of H345C mutant domain III/R. rubrum domain I mixture
33.3
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of R350C mutant domain III/R. rubrum domain I mixture
36.7
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of K424C mutant domain III/R. rubrum domain I mixture
40
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of D393C mutant domain III/R. rubrum domain I mixture
51.7
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of A432C mutant domain III/R. rubrum domain I mixture
55
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of A348C mutant domain III/R. rubrum domain I mixture
81.7
reduced acetylpyridine adenine dinucleotide
-
cyclic reaction of wild-type domain III/R. rubrum domain I mixture
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.75
2'-AMP
-
competitive inhibition vs. acetylpyridine adenine dinucleotide
2.03
2'-AMP
-
uncompetitive inhibition vs. acetylpyridine adenine dinucleotide
0.68
5'-AMP
-
competitive inhibition vs. acetylpyridine adenine dinucleotide
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0013
-
unpurified native enzyme, at pH 7.5, temperature not specified in the publication
0.0052
-
unpurified recombinant enzyme, at pH 7.5, temperature not specified in the publication
0.022
-
purified native enzyme, at pH 7.5, temperature not specified in the publication
0.0299
-
purified recombinant enzyme, at pH 7.5, temperature not specified in the publication
0.1
0.11
-
with oxidized acetyl pyridine adenine dinucleotide and deamino-NADPH as substrates, at pH 6.0 and 25°C
0.2
-
reduction of NADP+ by NADH driven by electron transport, cysteine-free enzyme reconstituted in membrane vesicles
0.3
-
membrane bound mutant enzyme with a 18 residues long linker between alpha and beta subunits
0.4
-
purified mutant enzyme with a 18 residues long linker between alpha and beta subunits, forward reaction
0.42
-
reduction of NADP+ by NADH driven by electron transport, wild-type enzyme reconstituted in membrane vesicles
0.47
-
with oxidized acetyl pyridine adenine dinucleotide and 1-N6-etheno-NADPH as substrates, at pH 6.0 and 25°C
0.6
-
membrane bound mutant enzyme with a 32 residues long linker between alpha and beta subunits
0.7
-
purified mutant enzyme with a 32 residues long linker between alpha and beta subunits, forward reaction
0.8
-
purified mutant enzyme with a direct linker between alpha and beta subunits, reverse reaction
1.46
-
with oxidized acetyl pyridine adenine dinucleotide and NADPH as substrates, at pH 6.0 and 25°C
1.9
-
reduction of acetylpyridine adenine dinucleotide by NADPH, cysteine-free enzyme reconstituted in membrane vesicles
10.8
3
-
reduction of acetylpyridine adenine dinucleotide by NADPH, wild-type enzyme reconstituted in membrane vesicles
3.9
-
purified mutant enzyme with a 18 residues long linker between alpha and beta subunits, reverse reaction
42
-
purified mutant enzyme with a 32 residues long linker between alpha and beta subunits, cyclic reaction
46
-
purified mutant enzyme with a 18 residues long linker between alpha and beta subunits, cyclic reaction
5.5
-
purified mutant enzyme with a 32 residues long linker between alpha and beta subunits, reverse reaction
7
-
purified mutant enzyme with a direct linker between alpha and beta subunits, cyclic reaction
0.1
-
membrane bound mutant enzyme with a direct linker between alpha and beta subunits
0.1
-
purified mutant enzyme with a direct linker between alpha and beta subunits, forward reaction
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
H91E mutant enzyme, optima for forward reaction below pH 5.5, 7% of wild-type enzyme activity at pH 6.0
6
-
reverse reaction catalyzed by H91E mutant enzyme, 20% of wild-type enzyme activity
7.1
-
pH optimum for the reduction of oxidized acetyl pyridine adenine dinucleotide by NADPH
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
titration of Escherichia coli transhydrogenase domain III with bound NADP+ or NADPH studied by NMR reveals no pH-dependent conformational change in the physiological pH range
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
P73496 i.e. subunit PntA, P73500 i.e. subunit PntB
UniProt
brenda
-
392594, 392618, 392619, 392662, 392663, 392664, 392665, 392667, 392668, 392671, 392672, 657468, 658003, 658197, 658712, 659274, 659437, 672321, 672325, 674194
-
-
brenda
-
-
-
brenda
P07001 i.e. subunit PntA, P0AB67 i.e. subunit PntB
UniProt
brenda
strain MG1655, wild type strain and enzyme deficient mutant, mutant strain displays very poor growth rates
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
found almost exclusively in the thylakoid membrane fraction
brenda
-
-
392619, 392668, 657468, 658003, 658197, 658712, 659274, 659437, 660435, 672325, 689135, 698677, 733148, 733317, 733369, 733374, 733380, 733850
brenda
-
the enzyme is composed of three components. The dI and dIII components, which house the binding site for NAD(H) and NADP(H), respectively, are peripheral to the membrane, and dII spans the membrane
brenda
-
-
658162, 658712, 659725, 673613, 674550, 687656, 698677, 733318, 733371, 733372, 733378, 733380, 733850
brenda
found almost exclusively in the thylakoid membrane fraction
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
metabolism
-
transhydrogenase PntAB is a major source of NADPH that is required for biosynthesis in Escherichia coli
metabolism
proton translocation and nucleotide exchange are tightly coupled by direct interactions between residue H664 and NADP(H), the attachment and detachment of NADP(H)-bound domain dIII is strictly dependent on the protonation state of H664 and opens the proton channel to the opposite sides of the membrane. The forward reaction occurs under a high proton motive force and an excess of NADP+. After hydride transfer, dIII-NADPH swivels down and attaches to dII-H664, opening it to the P side. This enables the protonation of H664 from the P side. Nucleotide exchange then follows. dIII-NADP+ detaches from dII-H664+, this opens dII to the N side where H664+ is deprotonated. Domain dIII-NADP+ then associates with dI, allowing for hydride transfer. All the steps can be easily reversed in the appropriate conditions
physiological function
-
the enzyme couples electron movement between the NADP/NADPH and NAD/NADH pools to the protonmotive force across the mitochondrial inner membrane
physiological function
disruption of subunit PntA results in phenotypic growth defects observed under low light intensities in the presence of glucose. Under autotrophic conditions the disruption mutant does not differ from the wild-type strain. The phenotypic defects of the mutant are accompanied by significant malfunction and damage of the photosynthetic machinery
physiological function
in a congenic mouse model carrying a mutated NNT gene, the absence of NNT activity results in lower total NADPH sources activity in the brain mitochondria of young mice, which is partially compensated in aged mice. Nonsynaptic mitochondria show higher NNT activity than synaptic mitochondria. In the absence of NNT, an increased release of H2O2 from mitochondria is observed when the metabolism of respiratory substrates occurs with restricted flux through relevant mitochondrial NADPH sources or when respiratory complex I is inhibited. Mitochondria from Nnt-/- brains are unable to sustain NADP in its reduced state when energized in the absence of carbon substrates
physiological function
in cardiac mitochondria from NNT-competent mice, H2O2 emission is equally low with pyruvate/malate or 2-oxoglutarate as substrates. In NNT-deficient mitochondria, H2O2 emission is higher with 2-oxoglutarate than with pyruvate/malate as substrate, and further potentiated by complex I blockade. NADH from 2-oxoglutarate dehydrogenase selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. In heart failure, 2-oxoglutarate dehydrogenase/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade
physiological function
NNT expression and activity are elevated in response to the mitochondrial dysfunction and oxidative stress associated with angiotensin II treatment. Knockdown of NNT leads to a significant elevation of mitochondrial ROS production and impaired glutathione peroxidase and glutathione reductase activities associated with a reduction in the NADPH/NADP+ ratio. Loss of NNT also promotes mitochondrial dysfunction, disruption of the mitochondrial membrane potential, and impaired ATP production in response to angiotensin II. The loss of NNT augments endothelial nitric oxide synthase phosphorylation at Ser1177, but neither endothelial nitric oxide synthase activity nor nitric oxide production are similarly increased
physiological function
NNT is largely responsible for the acute glucose-induced rise in pancreatic islet NADPH/NADP+ ratio and decrease in mitochondrial glutathione oxidation, with a small impact on cytosolic glutathione. These effects results from a glucose-dependent reduction in NADPH consumption by NNT reverse mode of operation, rather than from a stimulation of its forward mode of operation. Lack of NNT in islets decreases their sensitivity to exogenous H2O2 at non-stimulating glucose. The lack of NNT does not alter the glucose-stimulation of Ca2+ influx and upstream mitochondrial events, but it markedly reduces both phases of glucose stimulation of insulin secretion by altering Ca2+-induced exocytosis and its metabolic amplification
physiological function
NNT loss does not compromise the mitochondrial thioredoxin antioxidant system but compromises mitochondrial oxidative capacity. The activity of complex I-III is significantly reduced following NNT knockdown. NNT loss does not disrupt Fe-S cluster biosynthesis but is associated with decreases in mitochondrial Fe-S protein function and disrupts fatty acid metabolism
physiological function
NTH has an essential structural role in crystalloid biogenesis, whilst its enzymatic activity is required for sporozoite development. An enzyme null mutant develops normally in the mouse. NTH-KO parasites display normal gametocyte development, gametogenesis, and form ookinetes of normal size and shape. Pigment in these ookinetes is more dispersed and not found in clusters that surround and highlight the crystalloids. Absence of these pigment clusters is caused by loss of crystalloid formation. NTH-KO parasites developed oocyst numbers comparable to wild-type, but these oocysts fail to produce sporozoites
physiological function
overexpression of pyridine nucleotide transhydrogenase, PntAB, results in a significant increase in biomass and glycolic acid titer and yield. Improved redox homeostasis resulting from PntAB overexpression positively affects the anabolic rate of the cell. PntAB overexpression result in 154 and 37% increase in NAD+/NADH ratio, at 48 and 72 h, respectively, while the NADP+ concentrations are 70 and 30% lower at 24 and 72 h. Expression of PntAB in an optimized glycolic acid-producing strain improves the growth and product titer significantly
physiological function
pharmacological inhibition of complex CI, nicotinamide nucleotide transhydrogenase NNT and antioxidant system significantly decreases the ability of mitochondria to exhibit mitochondrial transition ROS spike (mTRS). NADH levels follow a similar trend to that of ROS during the mTRS. mTRS is enhanced by simultaneous activation of CI and complex II and NNT regulates mTRS via NADH- and membrane potential-dependent mechanisms. mTRS changes in amplitude under stress conditions and its occurrence can be a signature of mitochondrial health
physiological function
presence of NNT function is observed in detergent-solubilized and intact functional skeletal muscle mitochondria isolated from wild-type (NNT+/+) mice, but not in skeletal muscle mitochondria from congenic mice carrying a mutated NNT gene (NNT-/-). The NADPH supplied by NNT supports up to 600 pmol/mg/min of H2O2 removal under selected conditions. Skeletal muscle mitochondria from NNT-/- mice remove exogenous H2O2 at wild-type levels and exhibit a maintained or even decreased net emission of endogenous H2O2 when substrates that support Krebs cycle reactions are present (e.g., pyruvate plus malate or palmitoylcarnitine plus malate). The total activities of concurrent NADP+-reducing enzymes such as IDH2, malic enzymes and glutamate dehydrogenase are about 70% elevated in NNT mice. Respiratory rates are similar between skeletal muscle mitochondria from both NNT genotypes
physiological function
transient knockdown of NNT in NCI-H295R cells increases intracellular levels of oxidative stress, resulting in a pronounced suppression of cell proliferation, higher apoptotic rates, and sensitization of cells to chemically induced oxidative stress. Steroidogenesis is stimulated by NNT loss. In a stable NNT knockdown model in the same cell line, after long-term culture, cells adapt metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remains suppressed. This is associated with higher rates of oxygen consumption
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
48000
50000
54000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
heterodimer
tetramer
-
domain I, i.e. alpha1 to alpha404, and III i.e. beta260 to beta462, are exposed to the cytosol and contain the binding sites for NAD(H) and NAD(P)H, respectively, domain II, i.e. alpha405 to alpha 510, spans the membrane
trimer
additional information
-
the protein has three components: dI binds NADH, dIII binds NADP+, and dII spans the membrane. Transhydrogenase is a dimer of two dI-dII-dIII monomers. The two catalytic sites alternate during turnover
dimer
-
monomers consist of three domains dI, dII, and dIII located on two separate polypeptide chains
trimer
-
dI2dIII trimers formed in mixtures of recombinant dI and dIII domains
trimer
-
dimer of domain I combined with a domain III monomer, deduced from crystal structure
trimer
-
dI2dIII trimers formed in mixtures of recombinant dI and dIII domains
trimer
-
mixture of isolated domains dI and dIII forms dI2dIII trimers, formation of trimers also with Q132N mutant dI domain
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop method, crystal structures of the NAD(H)-binding domain I of transhydrogenase in the absence as well as in the presence of oxidized and reduced substrate. The structures are determined at 1.9-2.0 A resolution
NAD(H)-binding domain I in the absence and in the presence of NAD+ or NADH, hanging drop vapor diffusion method, using 0.2 M ammonium acetate, 0.1 M tri-sodium citrate dihydrate (pH 5.6) and 30% (w/v) PEG 4000
cryo-electron microscopy structure in different conformational states. The NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane
crystal structure of domain I i.e. alpha1 subunit, with and without bound NADH, 1.8 A resolution without NADH, 1.9 A with NADH bound
dI2dIII complex with bound NAD+ and NADP+, NADH and NADPH, and ADP-ribose and NADPH
dI2dIII1 complex with bound NAD+ and 1,4,5,6-tetrahydronicotinamide adenine dinucleotide phosphate the dI2dIII1 complex with bound ,4,5,6-tetrahydronicotinamide adenine dinucleotide and NADP+. dI is the NAD(H)-binding component of transhydrogenase. dIII is the NADP(H)-binding component
-
domain dIII, domain dI dimer and dI2dIII complex in the presence of limiting NADH using the vapor diffusion method
-
mutant enzymes are crystallized by the hanging drop vapor diffusion method, using in 16-24% (w/v) 8K-PEG, 20-150 mM (NH4)2SO4, 100mM MES, pH 6.0, and 10% (v/v) glycerol in the presence of 50 mM NAD+ and 5 mM NADP+
-
2.2 A crystal structure of the transmembrane domain at pH 6.5. Presence of transient water flows across a narrow pore and a hydrophobic region in the middle of the membrane channel with key residues His42alpha2 (chain A) being protonated and Thr214beta (chain B) displaying a conformational change, respectively, to gate the channel access to both cytoplasmic and periplasmic chambers
using 30% (w/v) PEG 400 in 0.1 M MES pH 6.5 with 0.1-0.4 M magnesium nitrate and 1 to 2.5% benzamidine hydrochloride
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A348C
-
mutation introduced into a cysteine-free mutant enzyme, mutant shows markedly reduced activity
A398C
-
the mutant with wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
A432C
C292T/C339T/C395S/C397T/C435S
-
cysteine of the alpha subunits replaced, similar activity as wild-type
C292T/C339T/C395S/C397T/C435S/C147S/C260S
-
all 7 cysteines of the enzyme, 5 localized in the alpha subunit and 2 in the beta subunit, are replaced, the cysteine-free mutant shows about 5fold more activity in the reduction of acetylpyridine adenine dinucleotide by NADH than wild-type, the cyclic reduction of acetylpyridine adenine dinucleotide by NADH via NADPH is 2-2.5fold more activ
D392C
-
the mutant shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
E124C
-
domian dII, strongly reduced reverse activity, no effect on cyclic activity
G245L
G249L
G252C
G252L
G408C
-
the mutant with wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
G430C
H91C
-
the mutant of the beta subunit is unable to undergo the conformational change that occurs on binding of the substrates NADP+ or NADPH. The mutant retains 12% of the hydride transfer activity while proton translocation is reduced to 7% compared to the wild type enzyme
H91D
-
the mutant of the beta subunit retains 15% of the hydride transfer activity while proton translocation is reduced to 9% compared to the wild type enzyme
H91K
H91N
-
the mutant of the beta subunit retains 80% of the hydride transfer activity while proton translocation is reduced to 7% compared to the wild type enzyme
H91R
-
mutation in domain II, leads to occlusion of NADP(H) at the NADP(H)-binding site of domain III
H91S
-
the mutant of the beta subunit is unable to undergo the conformational change that occurs on binding of the substrates NADP+ or NADPH. The mutant retains 19% of the hydride transfer activity while proton translocation is reduced to 11% compared to the wild type enzyme
H91T
-
the mutant of the beta subunit is unable to undergo the conformational change that occurs on binding of the substrates NADP+ or NADPH. The mutant retains 11% of the hydride transfer activity while proton translocation is reduced to 8% compared to the wild type enzyme
I406C
-
the mutant with 450% of wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
K424C
-
mutation introduced into a cysteine-free mutant enzyme, mutant shows markedly reduced activity
M409C
-
the mutant with 75% of wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
N222K
-
mutation in domain II, leads to occlusion of NADP(H) at the NADP(H)-binding site of domain III
N222R
-
mutation in domain II, leads to occlusion of NADP(H) at the NADP(H)-binding site of domain III
R425C
S237C
-
domian dII, slightly reduced reverse activity, no efect on cyclic activity
S250C
S251C
S404C
-
the mutant with 75% of wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
T393C
V411C
-
the mutant with 125% of wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
Y431C
-
the mutant with 450% of wild type activity shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
D135N
E155W
E155W/G173C
-
dIII domain, catalytic properties are similar to the wild type dIII, increased rate of reverse reaction
E155W/R165A
-
the mutations mutation do not significantly affect catalytic activity
M239F
-
the Km for APAD+ during reverse transhydrogenation is 6fold greater compared to the wild type. Cyclic transhydrogenation (in membranes and the recombinant system) is substantially more inhibited (84%) than either forward or reverse transhydrogenation
M293I
-
the Km for APAD+ during reverse transhydrogenation is 5fold greater compared to the wild type. Cyclic transhydrogenation (in membranes and the recombinant system) is substantially more inhibited (70%) than either forward or reverse transhydrogenation
Q132N
R127A
R127M
R165A
-
a higher concentration of the nucleotide is needed to achieve the half-maximal rate compared to with the wild type protein
S135A
-
mutation has no effect in binding affinity of either NAD+ or NADH
S138A
-
the mutant shows reduced activity compared to the wild type enzyme
Y146A
Y146F
Y171W
T214A
additional information
-
properties of a variety of mutant enzymes containing modified conserved and semiconserved basic and acidic residues in the beta subunit
A432C
-
mutation in domain III, reverse reaction in the presence of domain I from R. rubrum, 150% higher reaction rate than wild-type domain III/R. rubrum domain I mixture
A432C
-
the mutant shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
G430C
-
mutation in domain III, reverse reaction in the presence of domain I from R. rubrum, 850% higher reaction rate than wild-type domain III/R. rubrum domain I mixture
G430C
-
the mutant shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
H91K
-
mutation in domain II, leads to occlusion of NADP(H) at the NADP(H)-binding site of domain III
H91K
-
the mutant of the beta subunit is present in the NADP(H)-induced conformation even in the absence of these substrates. The mutant retains 4% of the hydride transfer activity while proton translocation is reduced to 20% compared to the wild type enzyme
R425C
-
mutation introduced into a cysteine-free mutant enzyme, mutant shows markedly reduced activity
R425C
-
mutation in domain III, reverse reaction in the presence of domain I from R. rubrum, 425% higher reaction rate than wild-type domain III/R. rubrum domain I mixture
T393C
-
mutation in domain III, reverse reaction in the presence of domain I from R. rubrum, 175% higher reaction rate than wild-type domain III/R. rubrum domain I mixture
T393C
-
the mutant shows increased ratios between the rates of the forward and reverse reactions, thus approaching that of the wild type enzyme
D135N
-
mutation has no effect in binding affinity of either NAD+ or NADH
D135N
-
the mutant shows reduced activity compared to the wild type enzyme
E155W
-
mutation in domain III, similar catalytic activities as wild-type, used for tryptophan fluorescence measurements
E155W
-
dIII domain, catalytic properties are similar to the wild type dIII
E155W
-
the mutant shows reduced activity compared to the wild type enzyme
Q132N
-
dI domain, no cyclic transhydrogenation activity in mixtures of domain dIII with the dI mutant, mutation has little effect on the NADH binding affinity
Q132N
-
the mutant shows reduced activity compared to the wild type enzyme
R127A
-
mutation strongly inhibits the rate of transhydrogenation and alters the nucleotide-binding properties of the dI protein. When dIR127A is reconstituted into the intact enzyme in membranes, transhydrogenation rates are negligible. dI is the NAD(H)-binding component of the transhydrogenase
R127A
-
the mutant shows reduced activity compared to the wild type enzyme
R127M
-
mutation strongly inhibits the rate of transhydrogenation and alters the nucleotide-binding properties of the dI protein. When dIR127M is reconstituted into the intact enzyme in membranes, transhydrogenation rates are negligible. dI is the NAD(H)-binding component of the transhydrogenase
R127M
-
the mutant shows reduced activity compared to the wild type enzyme
Y146A
-
mutation in component dI that binds NADH. dI.Y146A more readily dissociates into monomers than wild-type dI. dI.Y146A monomers bind NADH much more weakly than dimers. dI.Y146A reconstitutes activity to dI-depleted membranes in its dimeric form but not in its monomeric form
Y146A
-
the mutant binds NADH much more weakly than the wild type enzyme
Y146F
-
mutation in component dI that binds NADH. Wild-type dI and dI.Y146F reconstituted activity to dI-depleted membranes with similar characteristics
Y171W
-
mutation in domain III, similar catalytic activities as wild-type, used for tryptophan fluorescence measurements
T214A
Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039
-
the mutant shows 5% or less of wild type activity
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
fusion protein is substantially more stable than wild type enzyme upon storage at 4°C
-
purified enzyme is inactivated at 4°C even in presence of dithiothreitol
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, 20 mM sodium tricine buffer, pH 7.6, 1 mM dithiothreitol, 0.2% Triton X-100, 30% glycerol, 4 weeks, no loss of activity
-
4°C, 50 mM Tris-HCl, pH 7.8, 1 mM, EDTA, 1 mM, dithiothreitol, 1 week, 10% loss of activity
-
4°C, fusion protein is substantially more stable than wild type enzyme upon storage
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
DEAE-Sepharose column chromatography and hydroxyapatite column chromatography
-
detergent-solubilized transhydrogenase, from isolated mitochondrial membranes, purified to apparent homogeneity using ion exchange and hydroxylapatite chromatographies. The isolated enzyme catalyzes neither NADH->NADP+ nor NADH->NAD+ transhydrogenations
phenyl-Sepharose column chromatography and DEAE-Trisacryl M column chromatography
-
purification of bacterially expressed, recombinant membrane protein fused with calmodulin-binding domains. This method allows isolation of the protein fusions in a single chromatography step using elution with the calcium chelating agent EDTA. Unlike purification of His-tagged proteins on nickel chelate, it is not sensitive to the presence of strong reducing agents (e.g., DTT). The protocol involves disruption of host bacteria by sonication, sedimentation of membranes by differential centrifugation, solubilization of membrane proteins and affinity chromatography on calmodulin-agarose. To achieve maximum purity and yield, the use of a combination of non-ionic and anionic detergents is suggested. Purification takes two working days, with an overnight wash of the column to increase the purity of the product
-
Q-Sepharose column chromatography, and butyl Toyopearl column chromatography
-
recombinant domain I
recombinant domain I and recombinant E155W and Y171W mutant domain III
-
the recombinant enzyme is purified by pre-extraction of the membranes with sodium cholate and Triton X-100, solubilization of the enzyme with sodium deoxycholate in the presence of 1 M potassium chloride, and centrifugation through a 1.1 M sucrose solution. The wild type enzyme is purified by phenyl Sepharose column chromatography, DEAE-Bio-Gel A column chromatography, and NAD+ agarose column chromatography
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
domain dI and His-tag fusion protein of dIII separately expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
expression of cysteine mutants A348C, A390C, K424C, and R425C in Escherichia coli
-
expression of domain I in Escherichia coli
expression of wild-type domain III, T393C, R425C, G430C and A432C mutant domain III in Escherichia coli
-
fusion protein with calmodulin-binding peptide and His-tag expressed in Escherichia coli JM109
-
the NADP(H)-binding enzyme portion is expressed in Escherichia coli BL21(DE3) cells
-
wild type dI and E155W and E155W/G173C mutants of dIII expressed in Escherichia coli
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
peripheral blood mononuclear cells from obese (BMI >30) compared to lean subjects have lower NNT and glutathione expression
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
synthesis
overexpression of pyridine nucleotide transhydrogenase, PntAB, results in a significant increase in biomass and glycolic acid titer and yield. Improved redox homeostasis resulting from PntAB overexpression positively affects the anabolic rate of the cell. PntAB overexpression result in 154 and 37% increase in NAD+/NADH ratio, at 48 and 72 h, respectively, while the the NADP+ concentrations are 70 and 30% lower at 24 and 72 h. Expression of PntAB in an optimized glycolic acid-producing strain improves the growth and product titer significantly
medicine
after 20 weeks on a high-fat diet, Nnt-/- mice exhibit a higher prevalence of steatohepatitis and content of liver triglycerides compared to Nnt+/+ mice on an identical diet. Under a a high-fat diet, the aggravated non-alcoholic fatty liver disease phenotype in the Nnt-/- mice is accompanied by an increased H2O2 release rate from mitochondria, decreased aconitase activity and higher susceptibility to Ca2+-induced mitochondrial permeability transition. A high-fat diet leads to the phosphorylation (inhibition) of pyruvate dehydrogenase and markedly reduces the ability of liver mitochondria to remove peroxide in Nnt-/- mice. Compared to mice that are chow-fed, a high-fat diet does not impair peroxide removal nor elicit redox imbalance in mitochondria from Nnt+/+ mice
medicine
in cardiac mitochondria from NNT-competent mice, H2O2 emission is equally low with pyruvate/malate or 2-oxoglutarate as substrates. In NNT-deficient mitochondria, H2O2 emission is higher with 2-oxoglutarate than with pyruvate/malate as substrate, and further potentiated by complex I blockade. NADH from 2-oxoglutarate dehydrogenase selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. In heart failure, 2-oxoglutarate dehydrogenase/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade
medicine
in peripheral blood mononuclear cells, palmitate decreases immune cell expression of NNT, NADPH, and anti-oxidant glutathione, but increases reactive oxygen and proinflammatory Th17 cytokines. Oleate has no effect on these outcomes. Genetic inhibition of NNT recapitulates the effects of palmitate. Peripheral blood mononuclear cells from obese (BMI >30) compared to lean subjects have lower NNT and glutathione expression, and higher Th17 cytokine expression, none of which are changed by exogenous palmitate
medicine
NNT activity is about 30% lower in cystic fibrosis cells than healthy cells. The cellular redox state, together with the low mitochondrial membrane potential, pushes to drive NNT reverse reaction, at the expense of its antioxidant potential, thus consuming NADPH to support NADH production. At the same time, the reduced NNT activity prevents the NADH, produced by the reaction, from causing an explosion of ROS by the damaged respiratory chain, in accordance with the reduced level of mitochondrial ROS in NNT-loss cells
medicine
NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression
medicine
transient knockdown of NNT in NCI-H295R cells increases intracellular levels of oxidative stress, resulting in a pronounced suppression of cell proliferation, higher apoptotic rates, and sensitization of cells to chemically induced oxidative stress. Steroidogenesis is stimulated by NNT loss. In a stable NNT knockdown model in the same cell line, after long-term culture, cells adapt metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remains suppressed. This is associated with higher rates of oxygen consumption
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Jackson, J.B.; Lever, T.M.; Rydstrm, J.; Persson, B.; Carlenor, E.
Proton-translocating transhydrogenase from photosynthetic bacteria
Biochem. Soc. Trans.
19
573-575
1991
Escherichia coli
brenda
Lever, R.M.; Palmer, T.; Cunningham, I.J.; Cotton, N.P.J.; Jackson, J.B.
Purification and properties of the H(+)-nicotinamide nucleotide transhydrogenase from Rhodobacter capsulatus
Eur. J. Biochem.
197
247-255
1991
Rhodobacter capsulatus
brenda
Cotton, N.P.J.; Lever, T.M.; Nore, B.F.; Jones, M.R.; Jackson, J.B.
The coupling between protonmotive force and the NAD(P)+ transhydrogenase in chromatophores from photosynthetic bacteria [published erratum appears in Eur J Biochem 1989 Oct 1;184(3):729]
Eur. J. Biochem.
182
593-603
1989
Rhodobacter capsulatus
brenda
Clarke, D.M.; Bragg, P.D.
Purification and properties of reconstitutively active nicotinamide nucleotide transhydrogenase of Escherichia coli
Eur. J. Biochem.
149
517-523
1985
Escherichia coli, Escherichia coli W-6
brenda
Clarke, D.M.; Bragg, P.D.
Cloning and expression of the transhydrogenase gene of Escherichia coli
J. Bacteriol.
162
367-373
1985
Escherichia coli, Escherichia coli MV-12
brenda
McFadden, B.J.; Fisher, R.R.
Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase: localization of substrate binding sites
Arch. Biochem. Biophys.
190
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1978
Rhodospirillum rubrum
brenda
Meuller, J.; Zhang, J.; Hou, C.; Bragg, P.D.; Rydstrom, J.
Properties of a cysteine-free proton-pumping nicotinamide nucleotide transhydrogenase
Biochem. J.
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Escherichia coli
brenda
Fjellstrm, O.; Axelsson, M.; Bizouarn, T.; Hu, X.; Johansson, C.; Meuller, J.; Rydstrm, J.
Mapping of residues in the NADP(H)-binding site of proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli
J. Biol. Chem.
274
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Escherichia coli, Rhodospirillum rubrum
brenda
Hu, X.; Zhang, J.; Fjellstrom, O.; Bizouarn, T.; Rydstrom, J.
Site-directed mutagenesis of charged and potentially proton-carrying residues in the beta subunit of the proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli. Characterization of the beta H91, beta D392, and beta K424 mutants
Biochemistry
38
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1999
Escherichia coli
brenda
Fjellstrom, O.; Bizouarn, T.; Zhang, J.W.; Rydstrom, J.; Venning, J.D.; Jackson, J.B.
Catalytic properties of hybrid complexes of the NAD(H)-binding and NADP(H)-binding domains of the proton-translocating transhydrogenases from Escherichia coli and Rhodospirillum rubrum
Biochemistry
38
415-422
1999
Escherichia coli, Rhodospirillum rubrum
brenda
Bergkvist, A.; Johansson, C.; Johansson, T.; Rydstrm, J.; Karlsson, g.
Interactions of the NADP(H)-binding domain III of proton-translocating transhydrogenase from Escherichia coli with NADP(H) and the NAD(H)-binding domain I studied by NMR and site-directed mutagenesis
Biochemistry
39
12595-12605
2000
Escherichia coli, Rhodospirillum rubrum
brenda
Bizouarn, T.; Fjellstrom, O.; Meuller, J.; Axelsson, M.; Bergkvist, A.; Johansson, C.; Goran Karlsson, B.; Rydstrom, J.
Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties
Biochim. Biophys. Acta
1457
211-228
2000
Escherichia coli
brenda
Cotton, N.P.; White, S.A.; Peake, S.J.; McSweeny, s.; Jackson, J.B.
The crystal structure of an asymmetric complex of the two nucleotide binding components of proton-translocating transhydrogenase
Structure
7
165-176
2001
Rhodospirillum rubrum
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brenda
Jeeves, M.; Smith, K.J.; Quirk, P.G.; Cotton, N.P.; Jackson, J.B.
Solution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from Rhodospirillum rubrum
Biochim. Biophys. Acta
15
248-257
2000
Rhodospirillum rubrum
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brenda
Bragg, P.D.; Hou, C.
The presence of an aqueous cavity in the proton-pumping pathway of the pyridine nucleotide transhydrogenase of Escherichia coli is suggested by the reaction of the enzyme with sulfhydryl inhibitors
Arch. Biochem. Biophys.
380
141-150
2000
Escherichia coli
brenda
Meuller, J.; Mjrn, K.; Karlsson, J.; Tigerstrm, a.; Rydstrm, J.; Hou, C.; Bragg, P.D.
Properties of a proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli with alpha and beta subunits linked through fused transmembrane helices
Biochim. Biophys. Acta
1506
163-171
2001
Escherichia coli
brenda
Rodrigues, D.J.; Venning, J.D.; Quirk, P.G.; Jackson, J.B.
A change in ionization of the NADP(H)-binding component (dIII) if proton-translocating transhydrogenase regulates both hydride transfer and nucleotide release
Eur. J. Biochem.
268
1430-1438
2001
Rhodospirillum rubrum
brenda
Prasad, G.S.; Wahlberg, M.; Sridhar, V.; Sundaresan, V.; Yamaguchi, M.; Hatefi, Y.; Stout, C.D.
Crystal structures of transhydrogenase domain I with and without bound NADH
Biochemistry
41
12745-12754
2002
Rhodospirillum rubrum (Q2RSB2)
brenda
Oswald, C.; Johansson, T.; Tornroth, S.; Okvist, M.; Krengel, U.
Crystallization and preliminary crystallographic analysis of the NAD(H)-binding domain of Escherichia coli transhydrogenase
Acta Crystallogr. Sect. D
60
743-745
2004
Escherichia coli
brenda
van Boxel, G.I.; Quirk, P.G.; Cotton, N.P.; White, S.A.; Jackson, J.B.
Glutamine 132 in the NAD(H)-binding component of proton-translocating transhydrogenase tethers the nucleotides before hydride transfer
Biochemistry
42
1217-1226
2003
Rhodospirillum rubrum
brenda
Karlsson, J.; Althage, M.; Rydstrom, J.
Roles of individual amino acids in helix 14 of the membrane domain of proton-translocating transhydrogenase from Escherichia coli as deduced from cysteine mutagenesis
Biochemistry
42
6575-6581
2003
Escherichia coli
brenda
Mather, O.C.; Singh, A.; van Boxel, G.I.; White, S.A.; Jackson, J.B.
Active-site conformational changes associated with hydride transfer in proton-translocating transhydrogenase
Biochemistry
43
10952-10964
2004
Rhodospirillum rubrum, Rhodospirillum rubrum (Q2RSB2), Homo sapiens (Q13423)
brenda
Rodrigues, D.J.; Jackson, J.B.
A conformational change in the isolated NADP(H)-binding component (dIII) of transhydrogenase induced by low pH: a reflection of events during proton translocation by the complete enzyme?
Biochim. Biophys. Acta
1555
8-13
2002
Rhodospirillum rubrum
brenda
Althage, M.; Bizouarn, T.; Kindlund, B.; Mullins, J.; Alander, J.; Rydstrom, J.
Cross-linking of transmembrane helices in proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli: implications for the structure and function of the membrane domain
Biochim. Biophys. Acta
1659
73-82
2004
Escherichia coli
brenda
Jackson, J.B.
Proton translocation by transhydrogenase
FEBS Lett.
545
18-24
2003
Escherichia coli, Rhodospirillum rubrum
brenda
Yamaguchi, M.; Stout, C.D.
Essential glycine in the proton channel of Escherichia coli transhydrogenase
J. Biol. Chem.
278
45333-45339
2003
Escherichia coli
brenda
Sauer, U.; Canonaco, F.; Heri, S.; Perrenoud, A.; Fischer, E.
The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli
J. Biol. Chem.
279
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2004
Escherichia coli
brenda
Sundaresan, V.; Chartron, J.; Yamaguchi, M.; Stout, C.D.
Conformational diversity in NAD(H) and interacting transhydrogenase nicotinamide nucleotide binding domains
J. Mol. Biol.
346
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2005
Rhodospirillum rubrum
brenda
Egorov, M.V.; Tigerstrom, A.; Pestov, N.B.; Korneenko, T.V.; Kostina, M.B.; Shakhparonov, M.I.; Rydstrom, J.
Purification of a recombinant membrane protein tagged with a calmodulin-binding domain: properties of chimeras of the Escherichia coli nicotinamide nucleotide transhydrogenase and the C-terminus of human plasma membrane Ca2+ -ATPase
Protein Expr. Purif.
36
31-39
2004
Escherichia coli
brenda
Pedersen, A.; Johansson, T.; Rydstroem, J.; Goeran Karlsson, B.
Titration of E. coli transhydrogenase domain III with bound NADP+ or NADPH studied by NMR reveals no pH-dependent conformational change in the physiological pH range
Biochim. Biophys. Acta
1707
254-258
2005
Escherichia coli
brenda
Bizouarn, T.; van Boxel, G.I.; Bhakta, T.; Jackson, J.B.
Nucleotide binding affinities of the intact proton-translocating transhydrogenase from Escherichia coli
Biochim. Biophys. Acta
1708
404-410
2005
Escherichia coli
brenda
Whitehead, S.J.; Rossington, K.E.; Hafiz, A.; Cotton, N.P.; Jackson, J.B.
Zinc ions selectively inhibit steps associated with binding and release of NADP(H) during turnover of proton-translocating transhydrogenase
FEBS Lett.
579
2863-2867
2005
Rhodospirillum rubrum
brenda
Iwaki, M.; Cotton, N.P.; Quirk, P.G.; Rich, P.R.; Jackson, J.B.
Molecular recognition between protein and nicotinamide dinucleotide in intact, proton-translocating transhydrogenase studied by ATR-FTIR Spectroscopy
J. Am. Chem. Soc.
128
2621-2629
2006
Escherichia coli
brenda
Brondijk, T.H.; van Boxel, G.I.; Mather, O.C.; Quirk, P.G.; White, S.A.; Jackson, J.B.
The role of invariant amino acid residues at the hydride transfer site of proton-translocating transhydrogenase
J. Biol. Chem.
281
13345-13354
2006
Rhodospirillum rubrum
brenda
Johansson, T.; Oswald, C.; Pedersen, A.; Toernroth, S.; Okvist, M.; Karlsson, B.G.; Rydstroem, J.; Krengel, U.
X-ray structure of domain I of the proton-pumping membrane protein transhydrogenase from Escherichia coli
J. Mol. Biol.
352
299-312
2005
Escherichia coli (P07001), Escherichia coli
brenda
Bhakta, T.; Whitehead, S.J.; Snaith, J.S.; Dafforn, T.R.; Wilkie, J.; Rajesh, S.; White, S.A.; Jackson, J.B.
Structures of the dI2dIII1 complex of proton-translocating transhydrogenase with bound, inactive analogues of NADH and NADPH reveal active site geometries
Biochemistry
46
3304-3318
2007
Rhodospirillum rubrum
brenda
Obiozo, U.M.; Brondijk, T.H.; White, A.J.; van Boxel, G.; Dafforn, T.R.; White, S.A.; Jackson, J.B.
Substitution of tyrosine 146 in the dI component of proton-translocating transhydrogenase leads to reversible dissociation of the active dimer into inactive monomers
J. Biol. Chem.
282
36434-36443
2007
Rhodospirillum rubrum
brenda
Pestov, N.B.; Rydstroem, J.
Purification of recombinant membrane proteins tagged with calmodulin-binding domains by affinity chromatography on calmodulin-agarose: example of nicotinamide nucleotide transhydrogenase
Nat. Protoc.
2
198-202
2007
Escherichia coli
brenda
Pedersen, A.; Karlsson, G.B.; Rydstroem, J.
Proton-translocating transhydrogenase: an update of unsolved and controversial issues
J. Bioenerg. Biomembr.
40
463-473
2008
Escherichia coli, Rhodospirillum rubrum
brenda
Anderlund, M.; Nissen, T.L.; Nielsen, J.; Villadsen, J.; Rydstroem, J.; Hahn-Haegerdal, B.; Kielland-Brandt, M.C.
Expression of the Escherichia coli pntA and pntB genes, encoding nicotinamide nucleotide transhydrogenase, in Saccharomyces cerevisiae and its effect on product formation during anaerobic glucose fermentation
Appl. Environ. Microbiol.
65
2333-2340
1999
Escherichia coli
brenda
Glavas, N.A.; Hou, C.; Bragg, P.D.
Involvement of histidine-91 of the beta subunit in proton translocation by the pyridine nucleotide transhydrogenase of Escherichia coli
Biochemistry
34
7694-7702
1995
Escherichia coli
brenda
Grimley, R.L.; Quirk, P.G.; Bizouarn, T.; Thomas, C.M.; Jackson, J.B.
Role of methionine-239, an amino acid residue in the mobile-loop region of the NADH-binding domain (domain I) of proton-translocating transhydrogenase
Biochemistry
36
14762-14770
1997
Rhodospirillum rubrum
brenda
Bizouarn, T.; Grimley, R.L.; Cotton, N.P.; Stilwell, S.N.; Hutton, M.; Jackson, J.B.
The involvement of NADP(H) binding and release in energy transduction by proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli
Biochim. Biophys. Acta
1229
49-58
1995
Escherichia coli
brenda
Bizouarn, T.; Stilwell, S.; Venning, J.; Cotton, N.P.J.; Jackson, J.B.
The pH dependences of reactions catalyzed by the complete proton-translocating transhydrogenase from Rhodospirillum rubrum, and by the complex formed from its recombinant nucleotide-binding domains
Biochim. Biophys. Acta
1322
19-32
1997
Rhodospirillum rubrum
brenda
Jeeves, M.; Smith, K.J.; Quirk, P.G.; Cotton, N.P.; Jackson, J.B.
Solution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from Rhodospirillum rubrum
Biochim. Biophys. Acta
1459
248-257
2000
Rhodospirillum rubrum
brenda
Bizouarn, T.; Althage, M.; Pedersen, A.; Tigerstroem, A.; Karlsson, J.; Johansson, C.; Rydstroem, J.
The organization of the membrane domain and its interaction with the NADP(H)-binding site in proton-translocating transhydrogenase from E. coli
Biochim. Biophys. Acta
1555
122-127
2002
Escherichia coli
brenda
Huxley, L.; Quirk, P.G.; Cotton, N.P.J.; White, S.A.; Jackson, J.B.
The specificity of proton-translocating transhydrogenase for nicotinamide nucleotides
Biochim. Biophys. Acta
1807
85-94
2011
Rhodospirillum rubrum
brenda
Jackson J.B, J.J.
A review of the binding-change mechanism for proton-translocating transhydrogenase
Biochim. Biophys. Acta
1817
1839-1846
2012
Escherichia coli, Rhodospirillum rubrum
brenda
Hutton, M.; Day, J.M.; Bizouarn, T.; Jackson, J.B.
Kinetic resolution of the reaction catalysed by proton-translocating transhydrogenase from Escherichia coli as revealed by experiments with analogues of the nucleotide substrates
Eur. J. Biochem.
219
1041-1051
1994
Escherichia coli
brenda
Johansson, C.; Pedersen, A.; Karlsson, B.G.; Rydstroem, J.
Redox-sensitive loops D and E regulate NADP(H) binding in domain III and domain I-domain III interactions in proton-translocating Escherichia coli transhydrogenase
Eur. J. Biochem.
269
4505-4515
2002
Escherichia coli
brenda
Quirk, P.G.; Jeeves, M.; Cotton, N.P.; Smith, J.K.; Jackson, B.J.
Structural changes in the recombinant, NADP(H)-binding component of proton translocating transhydrogenase revealed by NMR spectroscopy
FEBS Lett.
446
127-132
1999
Rhodospirillum rubrum
brenda
Jackson, J.B.; Peake, S.J.; White, S.A.
Structure and mechanism of proton-translocating transhydrogenase
FEBS Lett.
464
1-8
1999
Escherichia coli, Homo sapiens, Rhodospirillum rubrum
brenda
Murphy, M.P.
Redox modulation by reversal of the mitochondrial nicotinamide nucleotide transhydrogenase
Cell Metab.
22
363-365
2015
Mus musculus, Thermus thermophilus (Q72GS0), Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039 (Q72GS0)
brenda
Kaemaeraeinen, J.; Huokko, T.; Kreula, S.; Jones, P.R.; Aro, E.M.; Kallio, P.
Pyridine nucleotide transhydrogenase PntAB is essential for optimal growth and photosynthetic integrity under low-light mixotrophic conditions in Synechocystis sp. PCC 6803
New Phytol.
214
194-204
2017
Synechocystis sp. PCC 6803 (P73496 and P73500)
brenda
Leung, J.H.; Schurig-Briccio, L.A.; Yamaguchi, M.; Moeller, A.; Speir, J.A.; Gennis, R.B.; Stout, C.D.
Structural biology. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer
Science
347
178-181
2015
Thermus thermophilus
brenda
Figueira, T.; Francisco, A.; Ronchi, J.; dos Santos, G.; Santos, W.; Treberg, J.; Castilho, R.
NADPH supply and the contribution of NAD(P)+ transhydrogenase (NNT) to H2O2 balance in skeletal muscle mitochondria
Arch. Biochem. Biophys.
707
108934
2021
Mus musculus (Q61941)
brenda
Wagner, M.; Bertero, E.; Nickel, A.; Kohlhaas, M.; Gibson, G.; Heggermont, W.; Heymans, S.; Maack, C.
Selective NADH communication from alpha-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart
Basic Res. Cardiol.
115
53
2020
Mus musculus (Q61941)
brenda
Sharaf, M.S.; Stevens, D.; Kamunde, C.
Mitochondrial transition ROS spike (mTRS) results from coordinated activities of complex I and nicotinamide nucleotide transhydrogenase
Biochim. Biophys. Acta
1858
955-965
2017
Oncorhynchus mykiss (A0A060X964)
brenda
McCambridge, G.; Agrawal, M.; Keady, A.; Kern, P.; Hasturk, H.; Nikolajczyk, B.; Bharath, L.
Saturated fatty acid activates T cell inflammation through a nicotinamide nucleotide transhydrogenase (Nnt)-dependent mechanism
Biomolecules
9
79
2019
Homo sapiens (Q13423)
brenda
Saeed, S.; Tremp, A.Z.; Sharma, V.; Lasonder, E.; Dessens, J.T.
NAD(P) transhydrogenase has vital non-mitochondrial functions in malaria parasite transmission
EMBO Rep.
21
e47832
2020
Plasmodium berghei (A0A509AS70)
brenda
Chortis, V.; Taylor, A.E.; Doig, C.L.; Walsh, M.D.; Meimaridou, E.; Jenkinson, C.; Rodriguez-Blanco, G.; Ronchi, C.L.; Jafri, A.; Metherell, L.A.; Hebenstreit, D.; Dunn, W.B.; Arlt, W.; Foster, P.A.
Nicotinamide nucleotide transhydrogenase as a novel treatment target in adrenocortical carcinoma
Endocrinology
159
2836-2849
2018
Homo sapiens (Q13423)
brenda
Navarro, C.D.C.; Figueira, T.R.; Francisco, A.; DalBo, G.A.; Ronchi, J.A.; Rovani, J.C.; Escanhoela, C.A.F.; Oliveira, H.C.F.; Castilho, R.F.; Vercesi, A.E.
Redox imbalance due to the loss of mitochondrial NAD(P)-transhydrogenase markedly aggravates high fat diet-induced fatty liver disease in mice
Free Radic. Biol. Med.
113
190-202
2017
Mus musculus (Q61941)
brenda
Favia, M.; Atlante, A.
Cellular redox state acts as switch to determine the direction of NNT-catalyzed reaction in cystic fibrosis cells
Int. J. Mol. Sci.
22
967
2021
Homo sapiens (Q13423)
brenda
Ward, N.P.; Kang, Y.P.; Falzone, A.; Boyle, T.A.; DeNicola, G.M.
Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function
J. Exp. Med.
217
e20191689
2020
Homo sapiens (Q13423), Mus musculus (Q61941)
brenda
Cabulong, R.B.; Valdehuesa, K.N.G.; Banares, A.B.; Ramos, K.R.M.; Nisola, G.M.; Lee, W.K.; Chung, W.J.
Improved cell growth and biosynthesis of glycolic acid by overexpression of membrane-bound pyridine nucleotide transhydrogenase
J. Ind. Microbiol. Biotechnol.
46
159-169
2019
Escherichia coli (P07001 and P0AB67)
brenda
Francisco, A.; Ronchi, J.A.; Navarro, C.D.C.; Figueira, T.R.; Castilho, R.F.
Nicotinamide nucleotide transhydrogenase is required for brain mitochondrial redox balance under hampered energy substrate metabolism and high-fat diet
J. Neurochem.
147
663-677
2018
Mus musculus (Q61941)
brenda
Fu, Q.; Ma, R.; Fioravanti, C.F.
Purification of adult Hymenolepis diminuta (Cestoda) mitochondrial NADPH->NAD+ transhydrogenase
J. Parasitol.
105
321-329
2019
Hymenolepis diminuta (A0A564Y5E1)
brenda
Santos, L.R.B.; Muller, C.; de Souza, A.H.; Takahashi, H.K.; Spegel, P.; Sweet, I.R.; Chae, H.; Mulder, H.; Jonas, J.C.
NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic beta-cells
Mol. Metab.
6
535-547
2017
Mus musculus (Q61941)
brenda
Kampjut, D.; Sazanov, L.A.
Structure and mechanism of mitochondrial proton-translocating transhydrogenase
Nature
573
291-295
2019
Ovis aries (W5PFI3)
brenda
Rao, K.; Shen, X.; Pardue, S.; Krzywanski, D.
Nicotinamide nucleotide transhydrogenase (NNT) regulates mitochondrial ROS and endothelial dysfunction in response to angiotensin II
Redox Biol.
36
101650
2020
Homo sapiens (Q13423)
brenda
Padayatti, P.S.; Leung, J.H.; Mahinthichaichan, P.; Tajkhorshid, E.; Ishchenko, A.; Cherezov, V.; Soltis, S.M.; Jackson, J.B.; Stout, C.D.; Gennis, R.B.; Zhang, Q.
Critical role of water molecules in proton translocation by the membrane-bound transhydrogenase
Structure
25
1111-1119
2017
Thermus thermophilus (Q72GR9), Thermus thermophilus DSM 7039 (Q72GR9)
brenda
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