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Information on EC 1.8.1.14 - CoA-disulfide reductase
for references in articles please use BRENDA:EC1.8.1.14
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EC Tree 1 Oxidoreductases
1.8 Acting on a sulfur group of donors
1.8.1 With NAD+ or NADP+ as acceptor
1.8.1.14 CoA-disulfide reductase
IUBMB Comments
A flavoprotein. Not identical with EC 1.8.1.6 (cystine reductase), EC 1.8.1.7 (glutathione-disulfide reductase) or EC 1.8.1.13 (bis-γ-glutamylcystine reductase). The enzyme from the bacterium Staphylococcus aureus has a strong preference for NADPH , while the bacterium Bacillus megaterium contains both NADH and NADPH-dependent enzymes .
The expected taxonomic range for this enzyme is: Bacteria, Archaea
- 1.8.1.14
- staphylococcus
- aureus
- coash
- burgdorferi
- horikoshii
- borrelia
- polysulfide
-
mallett
- rhodanese
- furiosus
-
claiborne
- anthracis
-
spirochetal
-
fad-dependent
-
fahey
-
multiwavelength
-
nadph-binding
- persulfide
-
nymphs
-
enzootic
-
newton
-
karplus
-
nucleotide-disulfide
showSynonyms
coadr, coenzyme a-disulfide reductase, coenzyme a disulfide reductase, bb0728, bacoadr, coa disulfide reductase, coenzyme a disulphide reductase, coa-disulfide reductase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
BB0728
CoA-disulfide reductase (NADH)
-
-
-
-
CoA-disulfide reductase (NADH2)
-
-
-
-
CoADR
coenzyme A disulfide reductase
coenzyme A disulphide reductase
coenzyme A-disulfide reductase
EC 1.6.4.10
-
-
formerly
-
NADH-dependent coenzyme A disulfide reductase
NADH2:CoA-disulfide oxidoreductase
-
-
-
-
NADH:CoA-disulfide oxidoreductase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 CoA + NADP+ = CoA-disulfide + NADPH + H+
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
CoA:NADP+ oxidoreductase
A flavoprotein. Not identical with EC 1.8.1.6 (cystine reductase), EC 1.8.1.7 (glutathione-disulfide reductase) or EC 1.8.1.13 (bis-gamma-glutamylcystine reductase). The enzyme from the bacterium Staphylococcus aureus has a strong preference for NADPH [3], while the bacterium Bacillus megaterium contains both NADH and NADPH-dependent enzymes [1].
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CAS REGISTRY NUMBER
COMMENTARY
206770-55-0
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
methyl methanethiolsulfonate + NAD(P)H + H+
? + NAD(P)+
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: both NADPH and NADH are used efficiently, preference for NADPH with Km-value about eightfold lower than for NADH, no substrate: dephospho-CoA
Products: -
Products: -
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADH + H+
2-nitro-5-thiobenzoate + NAD+
Substrates: -
Products: -
Products: -
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADH + H+
2-nitro-5-thiobenzoate + NAD+
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NAD(P)H + H+
CoA + NAD(P)+
-
Substrates: specific substrate
Products: -
Products: -
?
CoA-disulfide + NAD(P)H + H+
CoA + NAD(P)+
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADH + H+
2 CoA + NAD+
Substrates: the phCoADR structure has a narrower access channel for CoA substrates, which suggests that this restriction might be responsible for the poor activity toward the bulky CoA disulfide substrate
Products: -
Products: -
?
CoA-disulfide + NADH + H+
2 CoA + NAD+
Substrates: the phCoADR structure has a narrower access channel for CoA substrates, which suggests that this restriction might be responsible for the poor activity toward the bulky CoA disulfide substrate
Products: -
Products: -
?
CoA-disulfide + NADH + H+
2 CoA + NAD+
Substrates: the specific activity with CoA-disulfide as an electron acceptor is about 5fold higher than with menadione
Products: -
Products: -
?
CoA-disulfide + NADH + H+
2 CoA + NAD+
Substrates: the specific activity with CoA-disulfide as an electron acceptor is about 5fold higher than with menadione
Products: -
Products: -
?
CoA-disulfide + NADH + H+
CoA + NAD+
-
Substrates: Bacillus anthracis CoADR can use either pyridine nucleotide equally well
Products: -
Products: -
?
CoA-disulfide + NADH + H+
CoA + NAD+
-
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADH + H+
CoA + NAD+
-
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADH + H+
CoA + NAD+
-
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
2 CoA + NADP+
Substrates: the phCoADR structure has a narrower access channel for CoA substrates, which suggests that this restriction might be responsible for the poor activity toward the bulky CoA disulfide substrate
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
2 CoA + NADP+
Substrates: the phCoADR structure has a narrower access channel for CoA substrates, which suggests that this restriction might be responsible for the poor activity toward the bulky CoA disulfide substrate
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
CoA + NADP+
-
Substrates: Bacillus anthracis CoADR can use either pyridine nucleotide equally well
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
CoA + NADP+
-
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
CoA + NADP+
-
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
CoA + NADP+
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADPH + H+
CoA + NADP+
-
Substrates: reduction of CoA disulfide occurs through two steps: thiol-disulfide exchange with the active site cysteine, followed by flavin-mediated hydride transfer from NADPH to reduce the cysteine-CoA disulfide bond and regenerate the active site
Products: -
Products: -
?
menadione + NADH + H+
? + NAD+
Substrates: -
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CoA-disulfide + NAD(P)H + H+
CoA + NAD(P)+
Substrates: -
Products: -
Products: -
?
CoA-disulfide + NADH + H+
CoA + NAD+
-
Substrates: -
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADH
-
both NADPH and NADH are used efficiently, preference for NADPH with Km-value about eightfold lower than for NADH
NADH
-
CoADR exhibits dual specificity with respect to the NAD(P)H substrate
NADPH
-
both NADPH and NADH are used efficiently, preference for NADPH with Km-value about eightfold lower than for NADH
NADPH
-
CoADR exhibits dual specificity with respect to the NAD(P)H substrate
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Infections
The coenzyme A disulphide reductase of Borrelia burgdorferi is important for rapid growth throughout the enzootic cycle and essential for infection of the mammalian host.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
CoA-disulfide
wild type enzyme, at 23°C, pH not specified in the publication
0.0286
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADH, wild-type enzyme
0.052
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADPH, wild-type enzyme
0.057
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADPH, mutant enzyme Y65A/Y66A/P67G/H367G
0.086
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADH, mutant enzyme Y65A/Y66A/P67G/H367G
0.047
methyl methanethiolsulfonate
mutant enzyme Y361F, at 23°C, pH not specified in the publication
0.078
methyl methanethiolsulfonate
wild type enzyme, at 23°C, pH not specified in the publication
0.575
methyl methanethiolsulfonate
mutant enzyme Y419F, at 23°C, pH not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.8
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADH, mutant enzyme Y65A/Y66A/P67G/H367G
4.4
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADPH, wild-type enzyme
5.43
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADH, wild-type enzyme
18.8
CoA-disulfide
pH 7.5, 75°C, wild-type enzyme, cosubstrate: NADPH, mutant enzyme Y65A/Y66A/P67G/H367G
27
CoA-disulfide
wild type enzyme, at 23°C, pH not specified in the publication
1.2
methyl methanethiolsulfonate
mutant enzyme Y419F, at 23°C, pH not specified in the publication
6.4
methyl methanethiolsulfonate
wild type enzyme, at 23°C, pH not specified in the publication
10.4
methyl methanethiolsulfonate
mutant enzyme Y361F, at 23°C, pH not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9000
CoA-disulfide
wild type enzyme, at 23°C, pH not specified in the publication
2.1
methyl methanethiolsulfonate
mutant enzyme Y419F, at 23°C, pH not specified in the publication
82
methyl methanethiolsulfonate
wild type enzyme, at 23°C, pH not specified in the publication
220
methyl methanethiolsulfonate
mutant enzyme Y361F, at 23°C, pH not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0003
(E)-2-(methylsulfonyl)ethenyl-CoA
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00004
(E)-2-(phenylsulfonyl)ethenyl-CoA
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00066
alpha,beta-unsaturated vinyl sulfone-CoA ethyl ester
wild type enzyme, at 37°C, pH not specified in the publication
0.00066
ethyl (2E)-prop-2-en-3-CoA-oate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.0003
methyl vinyl sulfone-CoA
wild type enzyme, at 37°C, pH not specified in the publication
0.00004
phenyl vinyl sulfone-CoA
wild type enzyme, at 37°C, pH not specified in the publication
0.00516
t-butyl (2E)-prop-2-en-3-CoA-oate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
no activity against oxidized glutathione and thioredoxin
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
spirochetes lacking CoADR exhibit a growth defect under both aerobic and anaerobic conditions. Enzyme loss affects survival of spirochete in fed, but not flat tick nymphs
malfunction
-
spirochetes lacking CoADR exhibit a growth defect under both aerobic and anaerobic conditions. Enzyme loss affects survival of spirochete in fed, but not flat tick nymphs
-
physiological function
-
the enzyme of Borrelia burgdorferi is necessary to maintain optimal redox ratios for CoA/CoA-disulfide and NAD+/NADH during periods of rapid replication throughout the enzootic cycle, to support thiol-disulfide homeostasis, and to indirectly protect the spirochete against peroxide-mediated membrane damage. The enzyme is also required for infectivity in mice
physiological function
-
the enzyme of Borrelia burgdorferi is necessary to maintain optimal redox ratios for CoA/CoA-disulfide and NAD+/NADH during periods of rapid replication throughout the enzootic cycle, to support thiol-disulfide homeostasis, and to indirectly protect the spirochete against peroxide-mediated membrane damage. The enzyme is also required for infectivity in mice
-
Show AA Sequence and Transmembrane Helices (104 entries)
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Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure at 2.30 A resolution. The structures of the NADH and NADPH complexes at ca. 2.3 A resolution reveal that a loop consisting of residues Glu180-Thr187 becomes ordered and changes conformation on NAD(P)H binding
-
sitting drop vapor diffusion method, using 16-26% 2-methyl-2,4-pentanediol, 0.2 M magnesium acetate, and 0.1 M sodium cacodylate, pH 6.5, at 15°C
-
sitting drop vapor diffusion method, using 35-37% (w/v) PEG 600, 0.3-0.4 M MgCl2, and 0.1 M HEPES, pH 7.5 (mutants Y361F and Y419F), or 27% (w/v) PEG 600, 0.4 M MgCl2, pH 7.2 (mutant Y361F/Y419F), or 31% (w/v) PEG 600, 0.4 M MgCl2, and 0.1 M HEPES, pH 7.2 (mutant C43S)
crystallization by vapor diffusion. X-ray structure is determined at 2.9 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Y367F
Y425F
Y65A/Y66A/P67G/H367G
C43S
the enzyme has ca. 0.03% activity relative to the wild type enzyme
Y361F
the mutant shows increased catalytic efficiency compared to the wild type enzyme
Y361F/Y419F
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
Y419F
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
Y367F
-
kcat for NADH is 3.9fold lower than wild-type value, kcat for NADPH is 5.6fold lower than wild-type value
Y425F
-
kcat for NADH is 30fold lower than wild-type value, kcat for NADPH is 93fold lower than wild-type value
Y65A/Y66A/P67G/H367G
the structure of the quadruple mutant shows a widened substrate channel, which is supported by a fourfold increase in kcat for the NAD(P)H-dependent reduction of CoA disulfide and enhanced activity toward the substrate at lower temperatures
Y65A/Y66A/P67G/H367G
-
the structure of the quadruple mutant shows a widened substrate channel, which is supported by a fourfold increase in kcat for the NAD(P)H-dependent reduction of CoA disulfide and enhanced activity toward the substrate at lower temperatures
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation adenosine 2',5'-diphosphate agarose column chromatography, and Ni-NTA column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli, wild-type and mutant enzymes C42S, and Y367F, Y425F, and Y367/Y425F
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Setlow, B.; Setlow, P.
Levels of acetyl coenzyme A, reduced and oxidized coenzyme A, and coenzyme A in disulfide linkage to protein in dormant germinated spores and growing and sporulating cells of Bacillus megaterium
J. Bacteriol.
132
444-452
1979
Priestia megaterium, Priestia megaterium QM
brenda
Harris, D.R.; Ward, D.E.; Feasel, J.M.; Lancaster, K.M.; Murphy, R.D.; Mallet, T.C.; Crane, E.J., 3rd
Discovery and characterization of a Coenzyme A disulfide reductase from Pyrococcus horikoshii. Implications for this disulfide metabolism of anaerobic hyperthermophiles
FEBS J.
272
1189-1200
2005
Pyrococcus horikoshii
brenda
Mallett, T.C.; Wallen, J.R.; Karplus, P.A.; Sakai, H.; Tsukihara, T.; Claiborne, A.
Structure of coenzyme A-disulfide reductase from Staphylococcus aureus at 1.54 A resolution
Biochemistry
45
11278-11289
2006
Staphylococcus aureus (O52582), Staphylococcus aureus
brenda
Hummel, C.S.; Lancaster, K.M.; Crane, E.J.
Determination of coenzyme A levels in Pyrococcus furiosus and other Archaea: implications for a general role for coenzyme A in thermophiles
FEMS Microbiol. Lett.
252
229-234
2005
Pyrococcus furiosus, Saccharolobus solfataricus, Thermococcus litoralis
brenda
Boylan, J.A.; Hummel, C.S.; Benoit, S.; Garcia-Lara, J.; Treglown-Downey, J.; Crane, E.J.; Gherardini, F.C.
Borrelia burgdorferi bb0728 encodes a coenzyme A disulphide reductase whose function suggests a role in intracellular redox and the oxidative stress response
Mol. Microbiol.
59
475-486
2006
Borreliella burgdorferi, Borreliella burgdorferi bb0728
brenda
Wallen, J.R.; Paige, C.; Mallett, T.C.; Karplus, P.A.; Claiborne, A.
Pyridine nucleotide complexes with Bacillus anthracis coenzyme A-disulfide reductase: a structural analysis of dual NAD(P)H specificity
Biochemistry
47
5182-5193
2008
Bacillus anthracis
brenda
Revell, K.D.; Heldreth, B.; Long, T.E.; Jang, S.; Turos, E.
N-Thiolated beta-lactams: Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus
Bioorg. Med. Chem.
15
2453-2467
2007
Staphylococcus aureus
brenda
van der Westhuyzen, R.; Strauss, E.
Michael acceptor-containing coenzyme A analogues as inhibitors of the atypical coenzyme A disulfide reductase from Staphylococcus aureus
J. Am. Chem. Soc.
132
12853-12855
2010
Staphylococcus aureus
brenda
Case, C.L.; Rodriguez, J.R.; Mukhopadhyay, B.
Characterization of an NADH oxidase of the flavin-dependent disulfide reductase family from Methanocaldococcus jannaschii
Microbiology
155
69-79
2009
no activity in Methanocaldococcus jannaschii
brenda
Wallace, B.D.; Edwards, J.S.; Wallen, J.R.; Moolman, W.J.; van der Westhuyzen, R.; Strauss, E.; Redinbo, M.R.; Claiborne, A.
Turnover-dependent covalent inactivation of Staphylococcus aureus coenzyme A-disulfide reductase by coenzyme A-mimetics: mechanistic and structural insights
Biochemistry
51
7699-7711
2012
Staphylococcus aureus (Q2FIA5), Staphylococcus aureus
brenda
Eggers, C.H.; Caimano, M.J.; Malizia, R.A.; Kariu, T.; Cusack, B.; Desrosiers, D.C.; Hazlett, K.R.; Claiborne, A.; Pal, U.; Radolf, J.D.
The coenzyme A disulphide reductase of Borrelia burgdorferi is important for rapid growth throughout the enzootic cycle and essential for infection of the mammalian host
Mol. Microbiol.
82
679-697
2011
Borreliella burgdorferi, Borreliella burgdorferi B31
brenda
Lencina, A.M.; Koepke, J.; Preu, J.; Muenke, C.; Gennis, R.B.; Michel, H.; Schurig-Briccio, L.A.
Characterization and X-ray structure of the NADH-dependent coenzyme A disulfide reductase from Thermus thermophilus
Biochim. Biophys. Acta Bioenerg.
1860
148080
2019
Thermus thermophilus (Q72HK3), Thermus thermophilus, Thermus thermophilus ATCC BAA-163 (Q72HK3)
brenda
Sea, K.; Lee, J.; To, D.; Chen, B.; Sazinsky, M.H.; Crane, E.J.
A broader active site in Pyrococcus horikoshii CoA disulfide reductase accommodates larger substrates and reveals evidence of subunit asymmetry
FEBS open bio
8
1083-1092
2018
Pyrococcus horikoshii (O58308), Pyrococcus horikoshii, Pyrococcus horikoshii ATCC 700860 (O58308)
brenda
EXTERNAL LINKS (specific for EC-Number 1.8.1.14)
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