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Information on EC 1.6.1.2 - NAD(P)+ transhydrogenase (Re/Si-specific) and Organism(s) Rhodospirillum rubrum and UniProt Accession Q2RSB4
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1.6.1.2 NAD(P)+ transhydrogenase (Re/Si-specific)IUBMB Comments
The enzyme from heart mitochondria is Re-specific with respect to NAD+ and Si-specific with respect to NADP+ [cf. EC 1.6.1.1 NAD(P)+ transhydrogenase (Si-specific)].
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Word Map
- 1.6.1.2
- nadp+
- rhodospirillum
- rubrum
-
hydride
-
transhydrogenation
-
nadh-binding
-
submitochondrial
-
chromatophores
- acetylpyridine
-
dihydronicotinamide
- isobutanol
- thio-nadp+
-
acpdad+
The taxonomic range for the selected organisms is: Rhodospirillum rubrum
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
pntab, energy-linked transhydrogenase, mitochondrial transhydrogenase, proton-translocating transhydrogenase, proton-translocating nicotinamide nucleotide transhydrogenase, nadph transhydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dII
-
-
-
-
dIII
-
-
-
-
energy-linked transhydrogenase
-
-
-
-
H+-thase
-
-
-
-
NAD transhydrogenase
-
-
-
-
NAD(P) transhydrogenase
-
-
-
-
NADH transhydrogenase
-
-
-
-
NADH-NADP-transhydrogenase
-
-
-
-
NADPH-NAD oxidoreductase
-
-
-
-
NADPH-NAD transhydrogenase
-
-
-
-
NADPH:NAD+ transhydrogenase
-
-
-
-
nicotinamide adenine dinucleotide (phosphate) transhydrogenase
-
-
-
-
nicotinamide nucleotide transhydrogenase
-
-
-
-
pyridine nucleotide transferase
-
-
-
-
pyridine nucleotide transhydrogenase
-
-
-
-
transhydrogenase
-
-
-
-
transhydrogenase, nicotinamide adenine dinucleotide (phosphate)
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NADPH + NAD+ = NADP+ + NADH
enzyme is stereospecific for the 4A hydrogen of NADH and the 4B hydrogen of NADPH
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NADPH:NAD+ oxidoreductase (Re/Si-specific)
The enzyme from heart mitochondria is Re-specific with respect to NAD+ and Si-specific with respect to NADP+ [cf. EC 1.6.1.1 NAD(P)+ transhydrogenase (Si-specific)].
CAS REGISTRY NUMBER
COMMENTARY
9014-18-0
not distinguished from EC 1.6.1.1
9072-60-0
not distinguished from EC 1.6.1.1
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
NADH + oxidized 3-acetylpyridine adenine dinucleotide
NAD+ + reduced 3-acetylpyridine adenine dinucleotide
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
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
-
synthesis of diphosphate from phosphate in chromatophores by reverse reaction
-
?
NADH + NADP+
NAD+ + NADPH
-
specific for 4A site of NADH, i.e. pro-R hydrogen and 4B site of NADPH, i.e. pro-S hydrogen
-
r
NADH + NADP+
NAD+ + NADPH
-
reaction is catalyzed by a mixture of recombinant human domain III and recombinant R. rubrum domain I
-
r
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, hydride ion equivalent is transferred from the A side of NC4 of NADH to the B side of NC4 of NADP+, provides NADPH for metabolic biosynthesis and reduction of glutathione
-
-
r
NADH + oxidized 3-acetylpyridine adenine dinucleotide
NAD+ + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
-
?
NADH + oxidized 3-acetylpyridine adenine dinucleotide
NAD+ + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
-
r
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
-
?
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
-
-
-
r
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
catalyzed by a mixture of purified recombinant domains I and III
-
r
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
enzyme also catalyzes a rapid, so called cyclic reaction, i.e. the reduction of acetylpyridine adenine dinucleotide in the presence of either NADP+ or NADPH: the NADPH/NADP+ remain permanently bound to domain III and are alternately oxidized by acetylpyridine adenine dinucleotide and then reduced by NADH in domain I
-
?
NADPH + oxidized 3-acetylpyridine adenine dinucleotide
NADP+ + reduced 3-acetylpyridine adenine dinucleotide
-
enzyme also catalyzes a rapid, so called cyclic reaction, i.e. the reduction of acetylpyridine adenine dinucleotide in the presence of either NADP+ or NADPH: the NADPH/NADP+ remain permanently bound to domain III and are alternately oxidized by acetylpyridine adenine dinucleotide and then reduced by NADH in domain I
-
?
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
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 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, hydride ion equivalent is transferred from the A side of NC4 of NADH to the B side of NC4 of NADP+, provides NADPH for metabolic biosynthesis and reduction of glutathione
-
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
-
NADH
-
-
NADP+
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-ethylmaleimide
-
inactivation of integral membrane bound component and soluble protein factor of enzyme from chromatophore, NADPH potentiates inactivation of the enzyme complex at low concentrations, NADP+ partially protects the intact complex and fully protects both components
Pentane-2,4-dione
-
inactivation of chromatophore complex, 156 mM, approx. 85% inactivation after 30 min, NADPH and NADP+ partially protect, half-maximal protection with 0.015 mM NADPH and 0.030 mM NADP+ respetively
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lysolecithin
-
aprrox. 0.3%, 150% activation of activity in chromatophore extracts
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.06
oxidized 3-acetylpyridine adenine dinucleotide
-
wild-type domain I
0.6
oxidized 3-acetylpyridine adenine dinucleotide
-
Y235F mutant of domain I
0.8
oxidized 3-acetylpyridine adenine dinucleotide
-
Y235N mutant of domain I
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
oxidized 3-acetylpyridine adenine dinucleotide
-
kcat for recombinant domain III in the presence of saturating amounts of domain I, reduction of acetylpyridine adenine dinucleotide by NADPH
1.44
oxidized 3-acetylpyridine adenine dinucleotide
-
kcat for recombinant domain I in the presence of saturating amounts of domain III, reduction of acetylpyridine adenine dinucleotide by NADPH
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
enzyme is compromised of a membrane-bound component and an easily dissociable soluble factor
-
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
trimer
-
trimers of dI2dIII1 are formes in mixed solutions containing dI and dIII domains
?
-
domain I contains the binding site for NAD+ and NADH, domain III for NADP+ and NADPH
?
-
domain I exists as a seperate polypeptide that can be removed from everted membrane vesicle i.e. chromatophores
dimer
-
monomer is split into PntAA, PntAB, and PntB chain, enzyme displays an overall dimeric structure, dI dimers are formed in solutions of isolated dI domains
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E155W
-
dIII domain, displays similar catalytic properties as wild type, introduced tryptophan fluorescence is sensitive to the redox state of the bound nucleotide
Y235F
Y235N
Y235F
-
mutant domain I/wild-type domain III mixtures catalyse acetylpyridine adenine dinucleotide reduction with similar rates as wild-type domain I/wild-type domain III mixtures
Y235F
-
mutation resides in the soluble NAD(H)-binding peripheral membrane subunit, i.e. domain I, reconstitution of depleted membranes with mutant domain I gives 44% of activity that is obtained with wild-type domain I reconstituted membranes
Y235N
-
mutation resides in the soluble NAD(H)-binding peripheral membrane subunit, i.e. domain I, reconstitution of depleted membranes with mutant domain I gives 18% of activity that is obtained with wild-type domain I reconstituted membranes
Y235N
-
mutant domain I/wild-type domain III mixtures catalyse acetylpyridine adenine dinucleotide reduction with similar rates as wild-type domain I/wild-type domain III mixtures
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
incubation of depleted membranes, inactivation of membrane transhydrogenase component
50
-
complete protection in the presence of NADPH, half-maximal protection with 0.01 mM NADPH
53
-
incubation for 3 min, 10 mM Mg2+ almost completely protect from inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
solubilized membrane component is unstable loosing all activity when stored overnight at 4°C or -70°C, stable at -70°C in the presence of 0.025 mM NADP+ for several months, inactivation by refreezing after thawing
-
trypsinolysis is stimulated several fold by NADPH and NADP+, half-maximal stimulation with 0.001-0.002 mM NADPH and 0.002-0.003 mM NADP+, Mg2+ protects from NADP+ stimulated inactivation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C or 4°C, Rhodospirillum rubrum membrane component, inactivation in 1 day, stabilization by NADP+
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of domain I Y235N and Y235F mutants in Escherichia coli
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nore, B.F.; Husain, I.; Nyren, P.; Baltscheffsky, M.
Synthesis of pyrophosphate coupled to the reverse energy-linked transhydrogenase reaction in Rhodospirillum rubrum chromatophores
FEBS Lett.
200
133-138
1986
Rhodospirillum rubrum
Jacobs, E.; Fisher, R.R.
Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase: chemical modification with N-ethylmaleimide and 2,4-pentanedione
Biochemistry
18
4315-4322
1979
Rhodospirillum rubrum
Jacobs, E.; Heriot, K.; Fisher, R.R.
Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. II. Solubilization of the membrane-bound component
Arch. Microbiol.
115
151-156
1977
Rhodospirillum rubrum
Rydstrm, J.
Energy-linked nicotinamide nucleotide transhydrogenases
Biochim. Biophys. Acta
463
155-184
1977
Bos taurus, Escherichia coli, Rattus norvegicus, Rhodospirillum rubrum
Fisher, R.R.; Rampey, S.A.; Sadighi, A.; Fisher, K.
Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. Proteolytic and thermal inactivation of the membrane component
J. Biol. Chem.
250
819-825
1975
Rhodospirillum rubrum
Diggle, C.; Bizouarn, T.; Cotton, N.P.; Jackson, J.B.
Properties of the purified, recombinant, NADP(H)-binding domain III of the proton-translocating nicotinamide nucleotide transhydrogenase from Rhodospirillum rubrum
Eur. J. Biochem.
241
162-170
1996
Rhodospirillum rubrum
Diggle, C.; Quirk, P.G.; Bizouarnt, T.; Grimley, R.L.; Cottont, N.P.J.; Thomas, C.M.; Jackson, J.B.
Mutation of Tyr235 in the NAD(H)-binding subunit of the proton-translocating nicotinamide nucleotide transhydrogenase of Rhodospirillum rubrum affects the conformational dynamics of a mobile loop and lowers the catalytic activity of the enzyme
J. Biol. Chem.
271
10109-10115
1996
Rhodospirillum rubrum
Bizouarn, T.; Grimley, R.; Diggle, C.; Thomas, C.M.; Jackson, J.B.
Mutations at tyrosine-235 in the mobile loop region of domain I protein of transhydrogenase from Rhodospirillum rubrum strongly inhibit hydride transfer
Biochim. Biophys. Acta
1320
265-274
1997
Bos taurus, Rhodospirillum rubrum
Peake, S.J.; Venning, J.D.; Jackson, J.B.
A catalytically active complex formed from the recombinant dI protein of Rhodospirillum rubrum transhydrogenase, and the recombinant dIII protein of the human enzyme
Biochim. Biophys. Acta
1411
159-169
1999
Homo sapiens, Rhodospirillum rubrum
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
Bos taurus, Escherichia coli, Rhodospirillum rubrum
Jackson, J.B.; White, S.A.; Quirk, P.G.; Venning, J.D.
The alternating site, binding change mechanism for proton translocation by Transhydrogenase
Biochemistry
41
4173-4185
2002
Bos taurus, Escherichia coli, Entamoeba histolytica, Homo sapiens, Rhodospirillum rubrum
Sundaresan, V.; Yamaguchi, M.; Chartron, J.; Stout, C.D.
Conformational change in the NADP(H) binding domain of transhydrogenase defines four states
Biochemistry
42
12143-12153
2003
Rhodospirillum rubrum (Q2RSB4), Rhodospirillum rubrum
Singh, A.; Venning, J.D.; Quirk, P.G.; van Boxel, G.I.; Rodrigues, D.J.; White, S.A.; Jackson, J.B.
Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation
J. Biol. Chem.
278
33208-33216
2003
Rhodospirillum rubrum, Homo sapiens (Q13423)
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
Jackson, J.B.; Leung, J.H.; Stout, C.D.; Schurig-Briccio, L.A.; Gennis, R.B.
Review and Hypothesis. New insights into the reaction mechanism of transhydrogenase Swivelling the dIII component may gate the proton channel
FEBS Lett.
589
2027-2033
2015
Bos taurus, Entamoeba histolytica, Thermus thermophilus, Rhodospirillum rubrum
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