Information on EC 1.1.1.87 - homoisocitrate dehydrogenase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
1.1.1.87
-
RECOMMENDED NAME
GeneOntology No.
homoisocitrate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
-
-
-
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
two enzyme groups act as acid-base catalysts in the reaction. A group with a pKa of 6.5-7 acts as a general base accepting a proton as the beta-hydroxy acid is oxidized to the beta-keto acid, and this residue participates in all three of the chemical steps, acting to shuttle a proton between the C2 hydroxyl and itself. The second group acts as a general acid with a pKa of 9.5 and likely catalyzes the tautomerization step by donating a proton to the enol to give the final product
-
retinol + NAD(P)+ = retinal + NAD(P)H + H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidative decarboxylation
-
-
-
-
reduction
-
-
-
-
reductive carboxylation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
coenzyme B biosynthesis
-
Lysine biosynthesis
-
lysine biosynthesis IV
-
lysine biosynthesis V
-
Metabolic pathways
-
Microbial metabolism in diverse environments
-
SYSTEMATIC NAME
IUBMB Comments
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate:NAD+ oxidoreductase (decarboxylating)
Forms part of the lysine biosynthesis pathway in fungi [3].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
(-)-1-hydroxy-1,2,4-butanetricarboxylate:NAD+ oxidoreductase (decarboxylating)
-
-
-
-
11-cis-RDH
Q8IZV5
-
11-cis-retinol dehydrogenase
Q8IZV5
-
2-hydroxy-3-carboxyadipate dehydrogenase
-
-
-
-
3-carboxy-2-hydroxyadipate dehydrogenase
-
-
-
-
3-carboxy-2-hydroxyadipate dehydrogenase
-
-
3-carboxy-2-hydroxyadipate:NAD+ oxidoreductase (decarboxylating)
-
-
-
-
atRDH
Q8HZT6
-
atRDH
Q8IZV5
-
atRDH
Q8VCH7
-
dehydrogenase, homoisocitrate
-
-
-
-
EC 1.1.1.155
-
-
formerly
-
HIc dehydrogenase
-
-
HICDH
Candida albicans ATCC 10231
-
-
-
HICDH
A4CYJ9
-
HICDH
Q5SIJ1
-
homoisocitrate dehydrogenase
-
-
homoisocitric dehydrogenase
-
-
-
-
isocitrate-homoisocitrate dehydrogenase
A4CYJ9
-
protein PH1722
A4CYJ9
-
RDH10
Q8HZT6
-
RDH10
Q8VCH7
-
retinol dehydrogenase 10
Q8IZV5
-
retinol dehydrogenase 10
Q8VCH7
-
CAS REGISTRY NUMBER
COMMENTARY
37250-23-0
-
9067-90-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
gene LYS12
-
-
Manually annotated by BRENDA team
Candida albicans ATCC 10231
gene LYS12
-
-
Manually annotated by BRENDA team
isoform Rdh10
-
-
Manually annotated by BRENDA team
isoform Rdh10
-
-
Manually annotated by BRENDA team
gene PH1722 or hdh
SwissProt
Manually annotated by BRENDA team
Saccharomycopsis lipolytica
-
-
-
Manually annotated by BRENDA team
strain HB27
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
Q5SIJ1
homoisocitrate dehydrogenase is involved in the alpha-aminoadipate pathway of lysine biosynthesis
additional information
-
three-dimensional structure and homology modeling, overview
additional information
Candida albicans ATCC 10231
-
three-dimensional structure and homology modeling, overview
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
Q5SIJ1
-
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
-
strict specificity for homoisocitrate
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
Q5SIJ1
i.e. (2R,3S)-homoisocitrate
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
-
strict specificity for homoisocitrate, the enzyme selectively binds the Mg(II):homoisocitrate complex
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
Candida albicans ATCC 10231
-
strict specificity for homoisocitrate, strict specificity for homoisocitrate, the enzyme selectively binds the Mg(II):homoisocitrate complex
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + NADH + H+ + CO2
show the reaction diagram
-
homoisocitrate dehydrogenase catalyzes the Mg2+- and K+-dependent oxidative decarboxylation of homoisocitrate to alpha-ketoadipate using NAD as the oxidant, it utilizes a Lys-Tyr pair to catalyze the acid-base chemistry of the reaction, the active site Lys-Tyr pair consists of lysine 206 and tyrosine 150
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + NADH + H+ + CO2
show the reaction diagram
-
substitution of potassium acetate for KCl changes the kinetic mechanism of HIcDH from a steady state random to a fully ordered mechanism with the binding of Mg-HIc followed by K+ and NAD+
-
-
?
(2R,3S)-3-(2-hydroxyethyl)malate + NAD+
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-(3-aminopropyl)malate + NAD+
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-(3-hydroxypropyl)malate + NAD+
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-(4-hydroxybutyl)malate + NAD+
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-(4-pentenyl)malic acid + NAD+
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-allylmalic acid + NAD+
?
show the reaction diagram
-
-
-
-
?
(2R,3S)-3-propylmalic acid + NAD+
?
show the reaction diagram
-
-
-
-
?
1-hydroxy-1,2,3-propanetricarboxylate + NAD+
?
show the reaction diagram
-
more effective substrate than 1-hydroxy-1,2,4-butanetricarboxylate
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
-
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-, ?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-, ?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
Saccharomycopsis lipolytica
-
-
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-, ?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
i.e. homoisocitrate
-
r
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
alpha-aminoadipate pathway for biosynthesis of lysine
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
Saccharomycopsis lipolytica
-
production of 2-oxoadipic acid, a precursor of lysine biosynthesis
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
involved in lysine biosynthesis through alpha-aminoadipate
-
-
?
11-cis-retinol + NAD+
11-cis-retinal + NADH + H+
show the reaction diagram
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity. RDH10 may function in the RPE retinoid visual cycle as an 11-cis-retinol dehydrogenase, and thereby partially compensate for the loss of RDH5 function in human patients with fundus albipunctatus
-
-
?
11-cis-retinol + NAD+
11-cis-retinal + NADH + H+
show the reaction diagram
-
microsomal preparations of RDH10 are not active in presence of NADP+
-
-
r
11-cis-retinol + NAD+
11-cis-retinal + NADH + H+
show the reaction diagram
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity
-
-
?
11-cis-retinol + NADP+
11-cis-retinal + NADPH
show the reaction diagram
-
-
-
-
?
11-cis-retinol + NADP+
11-cis-retinal + NADPH + H+
show the reaction diagram
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity. RDH10 may function in the RPE retinoid visual cycle as an 11-cis-retinol dehydrogenase, and thereby partially compensate for the loss of RDH5 function in human patients with fundus albipunctatus, RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity
-
-
?
2(R),3(S)-homoisocitrate + NAD+
alpha-ketoadipate + NADH + CO2 + H+
show the reaction diagram
-
with homoisocitrate as the substrate, no primary deuterium isotope effect is observed, and a small 13C kinetic isotope effect indicates that the decarboxylation step contributes only slightly to rate limitation
-
-
?
3-carboxy-2-hydroxyadipate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-, intermediate in lysine biosynthesis
-
-
?
3-isopropylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
3-isopropylmalate + NAD+
?
show the reaction diagram
A4CYJ9, -
-
-
-
?
3-vinylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
9-cis-retinol + NAD+
9-cis-retinal + NADH + H+
show the reaction diagram
-
microsomal preparations of RDH10 are not active in presence of NADP+
-
-
r
9-cis-retinol + NADP+
9-cis-retinal + NADPH
show the reaction diagram
-
-
-
-
?
all-trans retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
-
no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
-
-
r
all-trans retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
-
no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
-
-
r
all-trans-retinal + NADPH + H+
all-tans-retinol + NADP+
show the reaction diagram
-
-
-
-
r
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
-
RDH10 is a more efficient retinol dehydrogenase than a retinaldehyde reductase. Microsomal preparations of RDH10 are not active in presence of NADP+
-
-
r
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
-
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor. At assay conditions (pH 5.5 and pH 7.6), and NADH or NADPH is used as the cofactor, only a low level of all-trans retinol is generated by RDH10
-
-
r
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
Q8HZT6
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor. At assay conditions (pH 5.5 and pH 7.6), and NADH or NADPH is used as the cofactor, only a low level of all-trans retinol is generated by RDH10
-
-
r
all-trans-retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
-
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor. At assay conditions (pH 5.5 and pH 7.6), and NADH or NADPH is used as the cofactor, only a low level of all-trans retinol is generated by RDH10
-
-
r
all-trans-retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
Q8HZT6
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor. At assay conditions (pH 5.5 and pH 7.6), and NADH or NADPH is used as the cofactor, only a low level of all-trans retinol is generated by RDH10
-
-
r
all-trans-retinol + NADPH
all-trans-retinal + NADP+
show the reaction diagram
-
-
-
-
r
homoisocitrate + NAD+
?
show the reaction diagram
-
-
-
-
?
homoisocitrate + NAD+
?
show the reaction diagram
-
-
-
-
?
homoisocitrate + NAD+
?
show the reaction diagram
A4CYJ9, -
-
-
-
?
homoisocitrate + NAD+
?
show the reaction diagram
-
1.5fold preferred to isocitrate
-
-
?
homoisocitrate + NAD+
alpha-ketoadipate + NADH + CO2
show the reaction diagram
-
-
-
-
r
homoisocitrate + NAD+
alpha-ketoadipate + NADH + CO2 + H+
show the reaction diagram
-
-
-
-
r
isocitrate + NAD+
?
show the reaction diagram
-
-
-
-
r
isocitrate + NAD+
?
show the reaction diagram
-
-
-
-
?
isocitrate + NAD+
?
show the reaction diagram
A4CYJ9, -
-
-
-
?
isocitrate + NAD+
?
show the reaction diagram
-
20fold preferred to homoisocitrate
-
-
?
isocitrate + NAD+
? + NADH + H+
show the reaction diagram
-
low activity
-
-
?
threo-D-isocitric acid + NAD+
?
show the reaction diagram
-
with isocitrate as the substrate, primary deuterium and 13C isotope effects indicate that hydride transfer and decarboxylation steps contribute to rate limitation, and that the decarboxylation step is the more rate-limiting of the two. The multiple-substrate deuterium/13C isotope effects suggest a stepwise mechanism with hydride transfer preceding decarboxylation
-
-
?
trisodium (2S,3R)-2-(carboxylatomethoxy)-3-hydroxybutanedioate + NAD+
? + NADH + CO2
show the reaction diagram
-
-
-
-
?
trisodium (2S,3R)-2-[(carboxylatomethyl)amino]-3-hydroxybutanedioate + NAD+
? + NADH + CO2
show the reaction diagram
-
-
-
-
?
isopropylmalate + NAD+
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
catalyzes keto-enol tautomerization of tritiated alpha-ketoadipate, not: ethanol, isocitrate, malate, glutamate
-
-
-
additional information
?
-
-
no activity with 3-isopropylmalate
-
-
-
additional information
?
-
A4CYJ9, -
the enzyme is trifunctional performing the activities of 3-isopropylmalate, isocitrate, and homoisocitrate dehydrogenase in one pathway
-
-
-
additional information
?
-
-
no activity with isocitrate, isopropylmalate, and tartrate
-
-
-
additional information
?
-
-
no activity with tartrate
-
-
-
additional information
?
-
-
substrate binding site structure, the substrate specificity is determined by residue Arg85, no activity with 3-isopropylmalate
-
-
-
additional information
?
-
-
dual physiological role of isoform RDH10: in the biosynthesis of 11-cis-retinaldehyde for vision and in the biosynthesis of all-trans-retinoic acid for differentiation and development
-
-
-
additional information
?
-
-
retinol dehydrogenase 10 activity is critical for spatiotemporal synthesis of retinoic acid during embrogenesis
-
-
-
additional information
?
-
-
enzyme does not recognizes retinol bound to cellular retinol-binding protein type I as a substrate and functions exclusively in the oxidative reaction in cells
-
-
-
additional information
?
-
Q8IZV5
activation of peroxisome proliferator-activated receptor gamma induces the expression of RDH10
-
-
-
additional information
?
-
Q8VCH7
retinol to retinaldehyde conversion is the first step in the tissue-specific regulation of retinoic acid synthesis, at least in mammalian embryos
-
-
-
additional information
?
-
-
RDH10 does not oxidize 11-cis retinol, 9-cis retinol, or 13-cis retinol into the respective retinal (pH 7.6, in the presence of NAD or NADP+), indicating the substrate specificity of RDH10
-
-
-
additional information
?
-
Q8HZT6
RDH10 does not oxidize 11-cis retinol, 9-cis retinol, or 13-cis retinol into the respective retinal (pH 7.6, in the presence of NAD or NADP+), indicating the substrate specificity of RDH10
-
-
-
additional information
?
-
Candida albicans, Candida albicans ATCC 10231
-
substrate docking study
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
Q5SIJ1
-
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
-
strict specificity for homoisocitrate
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + NADH + H+ + CO2
show the reaction diagram
-
-
-
-
?
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
show the reaction diagram
Candida albicans ATCC 10231
-
strict specificity for homoisocitrate
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
-
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
-
r
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
alpha-aminoadipate pathway for biosynthesis of lysine
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
Saccharomycopsis lipolytica
-
production of 2-oxoadipic acid, a precursor of lysine biosynthesis
-
-
?
1-hydroxy-1,2,4-butanetricarboxylate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
involved in lysine biosynthesis through alpha-aminoadipate
-
-
?
11-cis-retinol + NAD+
11-cis-retinal + NADH + H+
show the reaction diagram
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity. RDH10 may function in the RPE retinoid visual cycle as an 11-cis-retinol dehydrogenase, and thereby partially compensate for the loss of RDH5 function in human patients with fundus albipunctatus
-
-
?
11-cis-retinol + NADP+
11-cis-retinal + NADPH + H+
show the reaction diagram
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity. RDH10 may function in the RPE retinoid visual cycle as an 11-cis-retinol dehydrogenase, and thereby partially compensate for the loss of RDH5 function in human patients with fundus albipunctatus
-
-
?
3-carboxy-2-hydroxyadipate + NAD+
2-oxoadipate + CO2 + NADH
show the reaction diagram
-
intermediate in lysine biosynthesis
-
-
?
3-isopropylmalate + NAD+
?
show the reaction diagram
A4CYJ9, -
-
-
-
?
homoisocitrate + NAD+
?
show the reaction diagram
A4CYJ9, -
-
-
-
?
isocitrate + NAD+
?
show the reaction diagram
A4CYJ9, -
-
-
-
?
additional information
?
-
A4CYJ9, -
the enzyme is trifunctional performing the activities of 3-isopropylmalate, isocitrate, and homoisocitrate dehydrogenase in one pathway
-
-
-
additional information
?
-
-
dual physiological role of isoform RDH10: in the biosynthesis of 11-cis-retinaldehyde for vision and in the biosynthesis of all-trans-retinoic acid for differentiation and development
-
-
-
additional information
?
-
-
retinol dehydrogenase 10 activity is critical for spatiotemporal synthesis of retinoic acid during embrogenesis
-
-
-
additional information
?
-
Q8IZV5
activation of peroxisome proliferator-activated receptor gamma induces the expression of RDH10
-
-
-
additional information
?
-
Q8VCH7
retinol to retinaldehyde conversion is the first step in the tissue-specific regulation of retinoic acid synthesis, at least in mammalian embryos
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD+
Saccharomycopsis lipolytica
-
-
NAD+
-
NADP+ can replace NAD+
NAD+
-
isoform RDH10 is strictly NAD+-dependent; microsomal preparations of RDH10 are not active in presence of NADP+
NAD+
-
no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
NAD+
Q8HZT6
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor
NAD+
-
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP+ as the cofactor
NAD+
-
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor
NAD+
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity
NADH
Saccharomycopsis lipolytica
-
-
NADH
-
no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
NADH
Q8HZT6
-
NADP+
-
NADP+ can replace NAD+
NADP+
-
no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
NADP+
Q8HZT6
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor
NADP+
-
the addition of NADP+ resulted in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP+ as the cofactor
NADP+
-
the addition of NADP+ results in more efficient oxidation of all-trans retinol into all-trans retinal, when compared with the addition of NAD+, suggesting that RDH10 prefers NADP as the cofactor
NADP+
-
RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity
NADPH
-
no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
NADPH
Q8HZT6
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K+
-
required for optimal activity
K+
Saccharomycopsis lipolytica
-
required for optimal activity
K+
-
dependent on
K+
-
dependent on
Mg2+
-
stimulation of oxidative decarboxylation, required for reductive carboxylation
Mg2+
Saccharomycopsis lipolytica
-
required
Mg2+
-
activation, 2fold activity at 5 mM
Mg2+
-
activates, increase in the affinity of enzyme for Mg-HIc as a result of elimination of the inhibitory effect of Cl-
Mg2+
-
dependent on
Mg2+
-
dependent on
Mg2+
Q5SIJ1
essentially required
Mn2+
-
stimulation of oxidative decarboxylation
Mn2+
Saccharomycopsis lipolytica
-
stimulation of oxidative decarboxylation
Mn2+
A4CYJ9, -
-
NH4+
-
activates
additional information
-
selectivity of the activator site for monovalent ions, K+ is the best activator, and NH4+ and Rb+ are also activators of the reaction, while Cs+, Li+, and Na+ are not, overview. Substitution of potassium acetate for KCl changes the kinetic mechanism of HIcDH from a steady state random to a fully ordered mechanism with the binding of Mg-HIc followed by K+ and NAD+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2R,3S)-3-(p-carboxybenzyl)malate
-
-
-
(2S,3S)-(-)-3-methylmercaptomalic acid
Q5SIJ1
-
-
(2S,3S)-thiahomoisocitrate
Q5SIJ1
interacts through hydrogen bonding to Arg 118, Tyr 125 and Lys 171 in the active site, enzme binding structure, overview
-
(R,E)-(3-carboxypropylidene)malic acid
-
competitive
(R,E)-(3-hydroxypropylidene)malic acid
-
competitive
(R,Z)-(3-carboxypropylidene)malic acid
-
competitive
(R,Z)-(3-hydroxypropylidene)malic acid
-
competitive
11-cis-retinol
-
substrate inhibition above 0.005 mM
2-oxoadipate
Saccharomycopsis lipolytica
-
-
3-carboxypropylidenemalate
-
-
3-[(carboxymethyl)sulfanyl]-2-oxopropanoic acid
-
-
9-cis-retinol
-
substrate inhibition above 0.001 mM
acetate
-
slight inhibition
all-trans-retinol
-
substrate inhibition
homoisocitrate
-
1.2 mM
homoisocitrate
Saccharomycopsis lipolytica
-
-
NAD+
-
substrate inhibition at high concentrations and in absence of K+, kinetics, overview
Oxaloglutarate
Saccharomycopsis lipolytica
-
-
thiahomocitrate
-
-
-
trisodium (2S,3R)-2-(carboxylatomethoxy)-3-hydroxybutanedioate
-
-
trisodium (2S,3R)-2-[(carboxylatomethyl)amino]-3-hydroxybutanedioate
-
-
trisodium (2S,3S)-2-[(carboxylatomethyl)sulfanyl]-3-hydroxybutanedioate
-
-
Mg-homoisocitrate
-
-
additional information
-
synthesis and inhibition potency of substrate analogue inhibitors derived from 3-hydroxyalkylidene- and 3-carboxyalkylidenemalate derivatives, overview
-
additional information
-
synthesis and inhibition potency of substrate analogue inhibitors derived from 3-hydroxyalkylidene- and 3-carboxyalkylidenemalate derivatives, overview, no inhibition by 3-vinylmalate
-
additional information
-
product and dead-end inhibition studies in the absence of K+
-
additional information
-
inhibitor docking study, molecular modeling of CaHIcDH-inhibitor interaction, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-oxoadipate
-
required for reductive carboxylation
cellular retinaldehyde-binding protein
-
RDH10 oxidizes 11-cis-retinol to generate 11-cis-retinaldehyde in vitro in the presence of cellular retinaldehyde-binding protein
-
NaHCO3-CO2
-
required for reductive carboxylation
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.074
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
recombinant His-tagged enzyme, pH 7.8, 20C
0.45
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
native enzyme, pH 7.8, 20C
7.5
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
Q5SIJ1
pH 7.8, 60C
0.59
-
(2R,3S)-3-(2-hydroxyethyl)malate
-
pH 7.8, 28C, recombinant enzyme
2.1
-
(2R,3S)-3-(2-hydroxyethyl)malate
-
pH 7.8, 36C, recombinant enzyme
0.51
-
(2R,3S)-3-(3-hydroxypropyl)malate
-
pH 7.8, 28C, recombinant enzyme
0.58
-
(2R,3S)-3-(3-hydroxypropyl)malate
-
pH 7.8, 36C, recombinant enzyme
0.44
-
(2R,3S)-3-(4-hydroxybutyl)malate
-
pH 7.8, 36C, recombinant enzyme
0.47
-
(2R,3S)-3-(4-hydroxybutyl)malate
-
pH 7.8, 28C, recombinant enzyme
2.7
-
(2R,3S)-3-(4-pentenyl)malic acid
-
pH 7.8, 28C, recombinant enzyme
9.4
-
(2R,3S)-3-(4-pentenyl)malic acid
-
pH 7.8, 36C, recombinant enzyme
0.41
-
(2R,3S)-3-allylmalic acid
-
pH 7.8, 36C, recombinant enzyme
2.8
-
(2R,3S)-3-allylmalic acid
-
pH 7.8, 28C, recombinant enzyme
0.29
-
(2R,3S)-3-propylmalic acid
-
pH 7.8, 36C, recombinant enzyme
0.78
-
(2R,3S)-3-propylmalic acid
-
pH 7.8, 28C, recombinant enzyme
0.4
-
1-hydroxy-1,2,3-propanetricarboxylate
-
purified enzyme, pH 8.0, 60C
7.5
-
1-hydroxy-1,2,4-butanetricarboxylate
-
purified enzyme, pH 8.0, 60C
0.06
-
11-cis-retinol
-
microsomal preparations of RDH10
1.4
-
3-carboxy-2-hydroxyadipate
-
-
1.33
-
3-isopropylmalate
-
pH 7.8, 25C, recombinant wild-type enzyme
0.083
-
3-vinylmalate
-
pH 7.8, 28C, recombinant enzyme
3.4
-
3-vinylmalate
-
pH 7.8, 36C, recombinant enzyme
0.04
-
9-cis-retinol
-
microsomal preparations of RDH10
6
-
9-cis-retinol
-
-
0.57
-
all-trans retinal
-
pH 7.4, 37C, wild-type enzyme
0.00018
-
all-trans retinol
-
pH 7.4, 37, mutynt enzyme S197A
0.0011
-
all-trans retinol
-
pH 7.4, 37C, mutant enzyme S197G
0.0041
-
all-trans retinol
-
pH 7.4, 37C, wild-type enzyme
0.4
-
all-trans-retinal
-
; microsomal preparations of RDH10
0.035
-
all-trans-retinol
-
; microsomal preparations of RDH10, cofactor: NAD+
1.5
-
alpha-ketoadipate
-
-
16.3
-
CO2
-
reductive carboxylation of alpha-ketoadipate
0.6
-
ethylmalate
-
pH 7.8, 36C, recombinant enzyme
1
-
ethylmalate
-
pH 7.8, 28C, recombinant enzyme
0.01
-
homoisocitrate
-
value below
0.018
-
homoisocitrate
-
pH 7.8, 36C, recombinant enzyme
0.018
-
homoisocitrate
-
-
0.0183
-
homoisocitrate
A4CYJ9, -
pH 7.8, 70C, recombinant enzyme
0.211
-
homoisocitrate
-
pH 7.8, 25C, recombinant wild-type enzyme
0.211
-
homoisocitrate
-
pH 7.8, 28C, recombinant enzyme
0.819
-
homoisocitrate
-
pH 7.8, 25C, recombinant mutant A80del
1
-
homoisocitrate
-
pH 7.8, 25C, recombinant mutant R87V
1.5
-
homoisocitrate
-
pH 7.8, 25C, recombinant mutant R87T
1.4
-
homoisocitric acid
-
-
0.0164
-
Isocitrate
A4CYJ9, -
pH 7.8, 70C, recombinant enzyme
0.161
-
Isocitrate
-
pH 7.5, 60C, recombinant mutant V135M
0.291
-
Isocitrate
-
pH 7.8, 25C, recombinant wild-type enzyme
0.291
-
Isocitrate
-
pH 7.8, 28C, recombinant enzyme
0.465
-
Isocitrate
-
pH 7.8, 25C, recombinant mutant A80del
0.521
-
Isocitrate
-
pH 7.5, 60C, recombinant wild-type enzyme
1.33
-
isopropylmalate
-
pH 7.8, 28C, recombinant enzyme
0.0042
-
Mg-homoisocitrate
-
oxidate decarboxylation of homoisocitrate
0.036
-
NAD+
-
pH 7.4, 37C, wild-type enzyme
0.042
-
NAD+
-
native enzyme, pH 7.8, 20C
0.1
-
NAD+
-
; microsomal preparations of RDH10
0.3
-
NAD+
-
pH 8.0, 25C, in presence of K+
0.45
-
NAD+
-
oxidate decarboxylation of homoisocitrate
1.09
-
NAD+
-
recombinant His-tagged enzyme, pH 7.8, 20C
9
-
NAD+
-
pH 8.0, 25C, in absence of K+
0.09
-
NADH
-
reductive carboxylation of alpha-ketoadipate
0.11
-
NADH
-
pH 7.4, 37C, wild-type enzyme
0.027
-
NADP+
-
pH 7.4, 37C, wild-type enzyme
0.015
-
NADPH
-
pH 7.4, 37C, wild-type enzyme
0.02
-
trisodium (2S,3R)-2-(carboxylatomethoxy)-3-hydroxybutanedioate
-
-
0.15
-
trisodium (2S,3R)-2-[(carboxylatomethyl)amino]-3-hydroxybutanedioate
-
-
3.2
-
Mg-homoisocitrate
-
reductive carboxylation of alpha-ketoadipate
additional information
-
additional information
-
substitution of potassium acetate for KCl changes the kinetic mechanism of HIcDH from a steady state random to a fully ordered mechanism with the binding of Mg-HIc followed by K+ and NAD+, increase in the affinity of enzyme for Mg-HIc as a result of elimination of the inhibitory effect of Cl-, kinetic analysis, overview
-
additional information
-
additional information
-
mutant enzymes kinetic analysis and pH-dependencies, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.38
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
recombinant His-tagged enzyme, pH 7.8, 20C
0.4
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
native enzyme, pH 7.8, 20C
0.78
-
(2R,3S)-3-(2-hydroxyethyl)malate
-
pH 7.8, 36C, recombinant enzyme
25
-
(2R,3S)-3-(2-hydroxyethyl)malate
-
pH 7.8, 28C, recombinant enzyme
4.8
-
(2R,3S)-3-(3-hydroxypropyl)malate
-
pH 7.8, 36C, recombinant enzyme
29
-
(2R,3S)-3-(3-hydroxypropyl)malate
-
pH 7.8, 28C, recombinant enzyme
2
8
(2R,3S)-3-(4-hydroxybutyl)malate
-
pH 7.8, 28C, recombinant enzyme
2.1
-
(2R,3S)-3-(4-hydroxybutyl)malate
-
pH 7.8, 36C, recombinant enzyme
0.14
-
(2R,3S)-3-(4-pentenyl)malic acid
-
pH 7.8, 36C, recombinant enzyme
3
-
(2R,3S)-3-(4-pentenyl)malic acid
-
pH 7.8, 28C, recombinant enzyme
0.34
-
(2R,3S)-3-allylmalic acid
-
pH 7.8, 36C, recombinant enzyme
37
-
(2R,3S)-3-allylmalic acid
-
pH 7.8, 28C, recombinant enzyme
0.7
-
(2R,3S)-3-propylmalic acid
-
pH 7.8, 36C, recombinant enzyme
53
-
(2R,3S)-3-propylmalic acid
-
pH 7.8, 28C, recombinant enzyme
171
-
1-hydroxy-1,2,3-propanetricarboxylate
-
purified enzyme, pH 8.0, 60C
171
-
1-hydroxy-1,2,4-butanetricarboxylate
-
purified enzyme, pH 8.0, 60C
0.371
-
3-isopropylmalate
-
pH 7.8, 25C, recombinant wild-type enzyme
0.5
-
3-vinylmalate
-
pH 7.8, 36C, recombinant enzyme
0.77
-
3-vinylmalate
-
pH 7.8, 28C, recombinant enzyme
0.61
-
ethylmalate
-
pH 7.8, 36C, recombinant enzyme
43
-
ethylmalate
-
pH 7.8, 28C, recombinant enzyme
5.46
-
homoisocitrate
-
pH 7.8, 25C, recombinant mutant A80del
13.7
-
homoisocitrate
A4CYJ9, -
pH 7.8, 70C, recombinant enzyme
17
-
homoisocitrate
-
pH 7.8, 36C, recombinant enzyme
17
-
homoisocitrate
-
-
20.8
-
homoisocitrate
-
pH 7.8, 25C, recombinant mutant R87V
27.8
-
homoisocitrate
-
pH 7.8, 25C, recombinant mutant R87T
46
-
homoisocitrate
-
pH 7.8, 28C, recombinant enzyme
46.2
-
homoisocitrate
-
pH 7.8, 25C, recombinant wild-type enzyme
10.9
-
Isocitrate
-
pH 7.8, 25C, recombinant mutant A80del
14.8
-
Isocitrate
A4CYJ9, -
pH 7.8, 70C, recombinant enzyme
42.8
-
Isocitrate
-
pH 7.8, 25C, recombinant wild-type enzyme
43
-
Isocitrate
-
pH 7.8, 28C, recombinant enzyme
211
-
Isocitrate
-
pH 7.5, 60C, recombinant mutant V135M
438
-
Isocitrate
-
pH 7.5, 60C, recombinant wild-type enzyme
0.37
-
isopropylmalate
-
pH 7.8, 28C, recombinant enzyme
0.38
-
NAD+
-
recombinant His-tagged enzyme, pH 7.8, 20C
0.4
-
NAD+
-
native enzyme, pH 7.8, 20C
0.59
-
trisodium (2S,3R)-2-(carboxylatomethoxy)-3-hydroxybutanedioate
-
-
2
-
trisodium (2S,3R)-2-[(carboxylatomethyl)amino]-3-hydroxybutanedioate
-
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5.16
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
recombinant His-tagged enzyme, pH 7.8, 20C
195659
8.75
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
native enzyme, pH 7.8, 20C
195659
0.35
-
NAD+
-
recombinant His-tagged enzyme, pH 7.8, 20C
14330
0.44
-
NAD+
-
native enzyme, pH 7.8, 20C
14330
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.013
-
(2S,3S)-thiahomoisocitrate
Q5SIJ1
pH 7.8, 60C
-
0.79
-
(R,E)-(3-carboxypropylidene)malic acid
-
pH 7.8, 36C, recombinant enzyme
3.1
-
(R,E)-(3-carboxypropylidene)malic acid
-
pH 7.8, 28C, recombinant enzyme
1.4
-
(R,E)-(3-hydroxypropylidene)malic acid
-
pH 7.8, 36C, recombinant enzyme
5.2
-
(R,E)-(3-hydroxypropylidene)malic acid
-
pH 7.8, 28C, recombinant enzyme
0.072
-
(R,Z)-(3-carboxypropylidene)malic acid
-
pH 7.8, 36C, recombinant enzyme
0.26
-
(R,Z)-(3-carboxypropylidene)malic acid
-
pH 7.8, 28C, recombinant enzyme
0.51
-
(R,Z)-(3-hydroxypropylidene)malic acid
-
pH 7.8, 36C, recombinant enzyme
15.3
-
(R,Z)-(3-hydroxypropylidene)malic acid
-
pH 7.8, 28C, recombinant enzyme
0.088
-
3-vinylmalate
-
pH 7.8, 28C, recombinant enzyme
12
-
3-[(carboxymethyl)sulfanyl]-2-oxopropanoic acid
-
-
0.002
-
Mg-homoisocitrate
-
oxidate decarboxylation of homoisocitrate
77
-
NAD+
-
pH 8.0, 25C, in absence of KOAc
0.01
-
trisodium (2S,3R)-2-(carboxylatomethoxy)-3-hydroxybutanedioate
-
-
0.000097
-
trisodium (2S,3S)-2-[(carboxylatomethyl)sulfanyl]-3-hydroxybutanedioate
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.97
-
(2R,3S)-3-(p-carboxybenzyl)malate
-
recombinant His-tagged enzyme, pH 7.8, 20C, competitive versus (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
-
3.78
-
(2R,3S)-3-(p-carboxybenzyl)malate
-
recombinant His-tagged enzyme, pH 7.8, 20C
-
0.000097
-
thiahomocitrate
-
recombinant His-tagged enzyme, pH 7.8, 20C
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.304
-
Saccharomycopsis lipolytica
-
-
564
-
-
purified enzyme, pH 8.0, 60C, with 1-hydroxy-1,2,4-butanetricarboxylate as substrate
8579
-
-
purified enzyme, pH 8.0, 60C, with 1-hydroxy-1,2,3-propanetricarboxylate as substrate
additional information
-
-
0.1 SE, 1 SE is change in absorption at wavelength 520 nm per 2 h per milligram of protein
additional information
-
-
mutant 18804 1.4 SE, 1 SE is change in absorption at wavelength 520 nm per 2 h per milligram of protein
additional information
-
-
several mutant with about 0.1 SE, 1 SE is change in absorption at wavelength 520 nm per 2 h per milligram of protein
additional information
-
-
1.2 SE, 1 SE is change in absorption at wavelength 520 nm per 2 h per milligram of protein
additional information
-
A4CYJ9, -
-
additional information
-
-
-
additional information
-
-
substrate specificity, recombinant enzyme, overview
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
reductive carboxylation
7.5
-
-
assay at
7.8
-
-
homocitrate + NAD+
7.8
-
A4CYJ9, -
assay at
7.8
-
-
assay at
7.8
-
Q5SIJ1
assay at
8.3
8.8
-
oxidative decarboxylation
additional information
-
-
mutant enzymes kinetics and pH-dependencies, overview
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.1
7.7
-
pH 6.1: about 60% of activity maximum, pH 7.7: about 50% of activity maximum, reductive carboxylation
6.5
8.5
-
activity drops sharply below pH 6.5 and above pH 8.5
7.4
9.3
-
pH 7.4: about 50% of activity maximum, pH 9.3: about 90% of activity maximum, oxidative decarboxylation
additional information
-
-
pH-rate profile in the absence of K+, overview
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
reductive carboxylation
7.5
-
-
oxidative decarboxylation
20
-
Saccharomycopsis lipolytica
-
assay at
20
-
-
assay at
60
-
-
assay at
60
-
Q5SIJ1
assay at
70
-
A4CYJ9, -
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
mRNA level of isoform Rdh10 declines during development, with strong and lasting expression in the meninges and choroid plexuses. Expression is also present in the striatum
Manually annotated by BRENDA team
Q8HZT6
low activity
Manually annotated by BRENDA team
-
mRNA level of isoform Rdh10 declines during development, with strong and lasting expression in the meninges and choroid plexuses. Expression is also present in the striatum
Manually annotated by BRENDA team
-
mRNA level of isoform Rdh10 declines during development, with strong and lasting expression in the meninges and choroid plexuses. Expression is also present in the striatum
Manually annotated by BRENDA team
-
inner ear, specific expression of isoform Rdh10 in the endolymphatic system and stria vascularis
Manually annotated by BRENDA team
-
expression of Rdh10 gene correlates with many sites of retinoid signalling during embryogenesis and organ differentiation
Manually annotated by BRENDA team
-
mRNA expression of isoform Rdh10 both in the prospective pigmented epithelium and neural retina
Manually annotated by BRENDA team
-
the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
-
strong expression, the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
Q8HZT6
low activity
Manually annotated by BRENDA team
-
strong expression, the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
Q8HZT6
low activity
Manually annotated by BRENDA team
-
a weak but detectable signal is present in normal lung, the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
Q8HZT6
low activity
Manually annotated by BRENDA team
-
mRNA level of isoform Rdh10 declines during development, with strong and lasting expression in the meninges and choroid plexuses. Expression is also present in the striatum
Manually annotated by BRENDA team
-
and vibrissae follicles, expression of isoform Rdh10 from early stages in regions where sensory receptors appear and mesenchymal/epithelial interactions take place
Manually annotated by BRENDA team
Q8HZT6
low activity
Manually annotated by BRENDA team
-
strong expression, the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
-
mRNA expression of isoform Rdh10 both in the prospective pigmented epithelium and neural retina
Manually annotated by BRENDA team
-
mRNA expression of isoform Rdh10 both in the prospective pigmented epithelium and neural retina
Manually annotated by BRENDA team
-
the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
Q8HZT6
low activity
Manually annotated by BRENDA team
-
the 3 kb isoform is the most abundant one
Manually annotated by BRENDA team
additional information
-
no expression in H-460 cells (non-small-cell lung cancer). Very low level of expression is detected in cell lines SKMES (squamous lung cancer) and SCLC (small-cell lung carcinoma)
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
38090
-
-
calculated from sequence
48000
-
-
gel filtration
48000
-
Saccharomycopsis lipolytica
-
native or denaturing PAGE
154000
-
-
recombinant enzyme, gel filtration
158000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 39600, SDS-PAGE and calculated
?
-
x * 38087, calculated from sequence
dimer
Saccharomycopsis lipolytica
-
2 * 48000, at high protein concentration or in presence of substrate the enzyme exists as dimer
tetramer
-
4 * 40000, recombinant enzyme, SDS-PAGE
tetramer
-
subunit interface, crystal structure analysis
tetramer
-
4 * 42600, SDS-PAGE, x * 41491, sequence calculation
tetramer
Candida albicans ATCC 10231
-
4 * 42600, SDS-PAGE, x * 41491, sequence calculation
-
monomer
Saccharomycopsis lipolytica
-
1 * 48000, native or denaturing PAGE
additional information
-
three-dimensional structure and homology modeling, overview
additional information
Candida albicans ATCC 10231
-
three-dimensional structure and homology modeling, overview
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme in binary complex with inhibitor (2S,3S)-thiahomoisocitrate, sitting drop vapour diffusion method, 0.00 ml of 8.7 mg/ml protein in 5 mM Tris-HCl, pH 7.8. 0.8 mM inhibitor, and 1.7 mM NAD, is mixed with 0.002 ml of reservoir solution containing 40% 2-methyl-2,4-pentandiol and 100mM citrate pH 4.85, eqilibration against 1 ml resetvoir solution, X-ray diffrcation structure determination and analysis at 2.6 A resolution, molecular replacement
Q5SIJ1
purified recombinant enzyme, hanging drop vapour diffusion method, 10 mg/ml protein with reservoir solution containing 24% PEG 400, and 0.1 M citrate, pH 4.8, addition of 0.003 ml drops of 0.1 M MgCl2, 5 mM isocitrate or homoisocitrate, and of a 0.001 ml drop 50 mM CdCl2, equilibration against 0.5 ml reservoir solution, 5 days at 20C, X-ray diffraction structure determination and analysis at 1.85 A resolution, molecular replacement
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
enzyme is stable when incubated for at least 15 min over the pH range of 5.0-10.0
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
90
-
-
half life: 16.7 h
93.6
-
-
melting point
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Mg2+ stabilizes
Saccharomycopsis lipolytica
-
Mn2+ stabilizes
Saccharomycopsis lipolytica
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, some loss of activity after repeated freeze-thawing cycles
-
-20C, ammonium sulfate precipitate, partially purified, stable
-
0C, potassium phosphate 20 mM, pH 7.2, 4-5 hours
-
-20C, stable as ammonium sulfate precipitate
Saccharomycopsis lipolytica
-
0C, pH 7.2, rapid loss of activity
Saccharomycopsis lipolytica
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain TOP 10F by nickel affinity chromatography'
-
recombinant enzyme from Escherichia coli strain OM17 by anion exchange and hydrophobic interaction chromatography, followed by another step of anion exchange chromatography
-
purification of His-tagged enzyme using nickel affinity chromatography results in an inactive enzyme
-
recombinnat His-tagged enzyme from Escherichia coli by metal affinity chromatography
A4CYJ9, -
recombinant enzyme from Escherichia coli by anion exchange chromatography and gel filtration
-
-
Saccharomycopsis lipolytica
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Q8HZT6
expression of His-tagged enzyme in Escherichia coli strain TOP 10F'
-
LYS1 gene codes for the alpha-aminoadipate pathway enzymes in fungi, can complement LYS1-deficient mutants of Candida albicans and Saccharomyces cerevisiae, amplification in Escherichia coli
-
DNA and amino acid sequence determination and analysis, overexpression in Escherichia coli strain OM17
-
expressed in COS1 cells
-
expression in Cos-1 cells
-
expression in Sf9 cell; RDH10 is expressed the enzyme in insect Sf9 cells using the Baculovirus expression system. Purification of RDH10-His6 from Sf9 cells using nickel affinity chromatography produces an inactive enzyme. Therefore, microsomal preparations of RDH10 are used for its kinetic characterization
-
RDH10 is expressed in COS cells
-
DNA and amino acid sequence determination and analysis, expression of His-tagged enzyme in Escherichia coli
A4CYJ9, -
expression in Escherichia coli
-
expressed in Escherichia coli BL21(DE3)
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
R87T
-
site-directed mutagenesis, the mutant oxidizes homoisocitrate, but not isocitrate and 3-isopropylmalate
R87V
-
site-directed mutagenesis, the mutant oxidizes homoisocitrate, but not isocitrate and 3-isopropylmalate
D169A
-
mutant enzyme completely loses enzymatic activity
D169N
-
mutant enzyme completely loses enzymatic activity
G43A/G47A/G49A
-
mutant enzyme completely loses enzymatic activity
K214A
-
mutant enzyme completely loses enzymatic activity
S197A
-
mutation does not abolish activity
S197C
-
mutant enzyme completely loses enzymatic activity
S197G
-
mutation does not abolish activity
S197T
-
mutant enzyme completely loses enzymatic activity
S197V
-
mutant enzyme completely loses enzymatic activity
Y210A
-
mutant enzyme completely loses enzymatic activity
K206M
-
site-directed mutagenesis, the active site mutant shows about 2400fold reduced activity compared to the wild-type enzyme, the Km for HIc does not change significantly
Y150F
-
site-directed mutagenesis, the active site mutant shows about 680fold reduced activity compared to the wild-type enzyme, the Km for HIc does not change significantly
R85V
-
complete loss of activity with isocitrate, significant activity with 3-isopropylmalate, no effect on activity with homoisocitrate
V135M
-
site-directed mutagenesis, tetramer-to-dimer structural transition enhances the activity with isocitrate 1.6fold
A80del
-
site-directed mutagenesis, the mutant shows altered substrate specificity preferring isocitrate to homoisocitrate, it is unable to oxidize 3-isopropylmalate, the specificity is similar to the enzyme from Thermus thermophilus
additional information
-
modulation of the broad substrate specificity of the trifunctional enzyme through site-directed mutagenesis, overview
K214R
-
mutant enzyme completely loses enzymatic activity
additional information
-
deletion of the two hydrophobic domains dissociates RDH10 from the membrane and abolishes its activity (mutants DELTA223, DELTA293329 and the double mutant lacking both of these regions)
Y210F
-
mutant enzyme completely loses enzymatic activity
additional information
-
trex mutant allele, T to C exchange at nucleotide 251. Midgestation lethal mutant which displays craniofacial, limb, and organ abnormalities due to insufficient retinoic acid signaling
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
detection of unique gene LYS1 for rapid identification of pathogenic fungi, LYS1 gene is a possible target for selective inhibition of growth of pathogenic fungi in vivo