Information on EC 1.1.1.31 - 3-hydroxyisobutyrate dehydrogenase

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

EC NUMBER
COMMENTARY
1.1.1.31
-
RECOMMENDED NAME
GeneOntology No.
3-hydroxyisobutyrate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-hydroxy-2-methylpropanoate + NAD+ = 2-methyl-3-oxopropanoate + NADH + H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
L-valine degradation I
-
-
Metabolic pathways
-
-
valine metabolism
-
-
Valine, leucine and isoleucine degradation
-
-
SYSTEMATIC NAME
IUBMB Comments
3-hydroxy-2-methylpropanoate:NAD+ oxidoreductase
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
beta-hydroxyisobutyrate dehydrogenase
-
-
-
-
HIBADH
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9028-39-1
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
; ATCC 14579; MmsB gene
-
-
Manually annotated by BRENDA team
Bacillus cereus ATCC14579
MmsB gene
-
-
Manually annotated by BRENDA team
IFO 0750
-
-
Manually annotated by BRENDA team
IFO 0750; IFO 1542
-
-
Manually annotated by BRENDA team
Corynebacterium hydrocarbons
-
-
-
Manually annotated by BRENDA team
Endomyces reessii
-
-
-
Manually annotated by BRENDA team
Nocardia lyena
-
-
-
Manually annotated by BRENDA team
Pseudomonas dacunhae
-
-
-
Manually annotated by BRENDA team
strain E23, recombinant enzyme expressed in Escherichia coli
SwissProt
Manually annotated by BRENDA team
Pseudomonas putida E23
E23
-
-
Manually annotated by BRENDA team
Pseudomonas putida E23
strain E23, recombinant enzyme expressed in Escherichia coli
SwissProt
Manually annotated by BRENDA team
Wistar rats
-
-
Manually annotated by BRENDA team
Trichosporon aculeatum
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
3-hydroxyisobutyrate dehydrogenase is a key enzyme for the metabolism of valine and some keto-bodies. It can catalyze reversible conversion of 3-hydroxyisobutyrate to methylmalonate semialdehyde
physiological function
-
3-hydroxyisobutyrate dehydrogenase is one of the critical enzymes generating glucose by metabolizing amino acids in the gluconeogenesis pathway. It participates in valine, leucine, and isoleucine degradation and is a central metabolic enzyme in the valine catabolic pathway. The enzyme plays an important role in regulating sperm motility and may serve as a novel sperm-motility marker
physiological function
Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
3-hydroxyisobutyrate dehydrogenase is a key enzyme for the metabolism of valine and some keto-bodies. It can catalyze reversible conversion of 3-hydroxyisobutyrate to methylmalonate semialdehyde
-
evolution
-
3-hydroxyisobutyrate dehydrogenase belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donors with NAD+ or NADP+ acceptors
additional information
-
enzyme activity of HIBADH in spermatozoa from patients with asthenozoospermia is reduced compared to controls
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-methyl-D,L-serine + NAD+
?
show the reaction diagram
Pseudomonas putida, Pseudomonas putida E23
-
-
-
-
?
3-hydroxy-2-methylpropanoate + NAD+
2-methyl-3-oxopropanoate + NADH + H+
show the reaction diagram
-
-
-
-
?
3-hydroxy-2-methylpropanoate + NAD+
2-methyl-3-oxopropanoate + NADH + H+
show the reaction diagram
Bacillus cereus, Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
-
-
-
r
3-hydroxy-2-methylpropanoate + NADP+
2-methyl-3-oxopropanoate + NADPH + H+
show the reaction diagram
Bacillus cereus, Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
-
-
-
r
3-hydroxyisobutyrate + NAD+
methylmalonate semialdehyde + NADH + H+
show the reaction diagram
-
-
-
-
r
3-hydroxyisobutyric acid + NAD+
methylmalonic semialdehyde + NADH
show the reaction diagram
-
-
-
-
r
3-hydroxypropionate + NAD(P)+
?
show the reaction diagram
Bacillus cereus, Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
is more active with NADP+ than NAD+
-
-
?
3-hydroxypropionate + NAD+
?
show the reaction diagram
-
-
-
-
?
3-hydroxypropionate + NAD+
?
show the reaction diagram
Pseudomonas putida, Pseudomonas putida E23
-
-
-
-
?
3-hydroxypropionate + NAD+
malonate semialdehyde + NADH + H+
show the reaction diagram
-
-
-
-
r
3-hydroxypropionate + NADP+
malonate semialdehyde + NADPH + H+
show the reaction diagram
-
-
-
-
r
D,L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
Pseudomonas aeruginosa, Pseudomonas dacunhae, Endomyces reessii, Nocardia lyena
-
-
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
strain IFO 1542
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
D-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
D-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
strain IFO 0750
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
-
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
-
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
r
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
Micrococcus luteus, Rhodotorula mucilaginosa, Micrococcus flavus, Corynebacterium hydrocarbons, Tsukamurella paurometabola, Trichosporon aculeatum
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
Pseudomonas putida E23
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
3-oxoisobutyrate + NADH
show the reaction diagram
Pseudomonas putida, Pseudomonas putida E23
Q59477
high stereospecificity
-
-
r
L-serine + NAD+
?
show the reaction diagram
Pseudomonas putida, Pseudomonas putida E23
-
-
-
-
?
additional information
?
-
-
the enzyme catalyzes the rate-limiting step in the irreversible degradative pathway for the carbon skeleton of valine and the other branched-chain amino acids
-
-
-
additional information
?
-
-
MmsB from Bacillus cereus exhibits 3-hydroxyisobutyrate dehydrogenase as well as 3-hydroxypropionate dehydrogenase activity, EC 1.1.1.59, wide substrate specificity of the 3-HIBADH
-
-
-
additional information
?
-
-
MmsB from Bacillus cereus exhibits 3-hydroxyisobutyrate dehydrogenase as well as 3-hydroxypropionate dehydrogenase activity, EC 1.1.1.59, wide substrate specificity of the 3-HIBADH
-
-
-
additional information
?
-
Bacillus cereus ATCC14579
-
MmsB from Bacillus cereus exhibits 3-hydroxyisobutyrate dehydrogenase as well as 3-hydroxypropionate dehydrogenase activity, EC 1.1.1.59, wide substrate specificity of the 3-HIBADH
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3-hydroxy-2-methylpropanoate + NAD+
2-methyl-3-oxopropanoate + NADH + H+
show the reaction diagram
-
-
-
-
?
3-hydroxy-2-methylpropanoate + NAD+
2-methyl-3-oxopropanoate + NADH + H+
show the reaction diagram
Bacillus cereus, Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
-
-
-
r
3-hydroxy-2-methylpropanoate + NADP+
2-methyl-3-oxopropanoate + NADPH + H+
show the reaction diagram
Bacillus cereus, Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
-
-
-
r
D,L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
Pseudomonas aeruginosa, Pseudomonas dacunhae, Endomyces reessii, Nocardia lyena
-
-
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
strain IFO 1542
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
D-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
D-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
strain IFO 0750
-
-
?
D,L-3-hydroxyisobutyrate + NAD+
2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
-
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
r
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
Micrococcus luteus, Rhodotorula mucilaginosa, Micrococcus flavus, Corynebacterium hydrocarbons, Tsukamurella paurometabola, Trichosporon aculeatum
-
-
-
-
?
L-3-hydroxyisobutyrate + NAD+
L-2-methyl-3-oxopropionate + NADH
show the reaction diagram
Pseudomonas putida E23
-
-
-
-
?
additional information
?
-
-
the enzyme catalyzes the rate-limiting step in the irreversible degradative pathway for the carbon skeleton of valine and the other branched-chain amino acids
-
-
-
additional information
?
-
Bacillus cereus, Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
MmsB from Bacillus cereus exhibits 3-hydroxyisobutyrate dehydrogenase as well as 3-hydroxypropionate dehydrogenase activity, EC 1.1.1.59
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD(P)+
-
is more active with NADP+ than NAD+
additional information
-
3-HIBADH is more active with NADP+ than NAD+
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
has no metal ion requirement, MnSO4, CuSO4, CaCl2, MgSO4, and FeSO4 have no effect; no metal ion requirement
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-3-hydroxy-2-methylpropanoate
-
competitive inhibitor of the S-isomer
HgCl2
-
-
NADH
-
product inhibition
p-chloromercuribenzoate
-
-
Zn2+
-
inhibits at 0.2 mM
ZnCl2
-
0.2 mM, 60% inhibition; inhibits approximately 60% of 3-HIBADH activity at 0.2 mM but shows no effect at 0.005 mM
iodoacetate
-
-
additional information
-
is not inhibited by 1-propanol, lactate potassium, malate potassium, malonate potassium, acetaldehyde, ethanol, and glycerin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
ethylene glycol tetraacetic acid or EDTA (all at 0.005 and 0.2 mM) do not affect 3-HIBADH activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
83
2-methyl-D,L-serine
-
-
0.12
3-hydroxyisobutyric acid
-
-
16.8
3-hydroxypropionate
-
; pH 8.5, 37C, KM-value for 3-hydroxyisobutyrate is approximately 20fold lower
18
3-hydroxypropionate
-
-
0.1
D,L-3-hydroxyisobutyrate
-
-
0.12
D,L-3-hydroxyisobutyrate
-
-
1.25
D-3-hydroxyisobutyrate
-
-
0.056
L-3-hydroxyisobutyrate
-
wild type, NAD as cofactor
0.061
L-3-hydroxyisobutyrate
-
-
0.104
L-3-hydroxyisobutyrate
-
wild type, NADP as cofactor
0.11
L-3-hydroxyisobutyrate
-
mutant D33R, NADP as cofactor
0.112
L-3-hydroxyisobutyrate
-
mutant D33R, NAD as cofactor
0.12
L-3-hydroxyisobutyrate
-
-
0.37
L-3-hydroxyisobutyrate
-
-
44
L-serine
-
-
0.022
NAD+
-
wild type
0.05
NAD+
-
-
0.054
NAD+
-
-
0.44
NAD+
-
-
0.5
NAD+
-
-
1.24
NAD+
-
mutant D33R
2.4
NAD+
-
; pH 8.5, 37C
0.24
NADP+
-
mutant D33R
0.25
NADP+
-
; pH 8.5, 37C
0.96
NADP+
-
wild type
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.49
(R)-3-Hydroxyisobutyrate
-
-
7.1
(S)-3-hydroxyisobutyrate
-
-
0.21
3-hydroxypropionate
-
; pH 8.5, 37C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0125
3-hydroxypropionate
-
pH 8.5, 37C
1632
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0037
-
index patient with 3-hydroxyisobutyric acidia
0.0042
-
patient 2 with 3-hydroxyisobutyric acidia
0.0046
-
patient 1 with 3-hydroxyisobutyric acidia
0.091
-
homogenate
8.7
-
purified enzyme
8.77
-
pH 8.5, 37C; purified enzyme, pH 8.5, 37C
20.9
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
-
assay at
8.8 - 9
-
; oxidation of 3-hydroxypropionate by 3-HIBADH
9 - 10.5
-
-
10
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 10
-
; oxidation of 3-hydroxypropionate by 3-HIBADH
7 - 11
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
-
assay at
37
-
; assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35 - 45
-
shows more than 90% of its optimized activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
astroglia-rich primary culture from neonatal rats
Manually annotated by BRENDA team
-
astroglia-rich primary culture from neonatal rats
Manually annotated by BRENDA team
-
elongating, elongated, and mature sperm
Manually annotated by BRENDA team
additional information
-
cell type-specific enzyme expression analysis, immunofluorescence labeling, overview
Manually annotated by BRENDA team
additional information
-
HIBADH is downregulated in low-motility sperm, and is enriched expressed during human spermiogenesis, quantitative RT-PCR expression analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
subcellular enzyme expression analysis, overview
-
Manually annotated by BRENDA team
additional information
-
the enzyme is located at the mid-piece (a specialized development from the mitochondria) of elongating, elongated, and mature sperm
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32000
-
gel filtration
695710
74000
-
gel filtration
286544
74000
-
-
286551
80000
-
gel filtration
286547
80000
-
-
286551
120000
-
gel filtration
286551
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 32000, SDS-PAGE
?
Q59477
x * 30280, deduced from gene sequence, x * 30300, SDS-PAGE
?
Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
x * 32000, SDS-PAGE
-
?
Pseudomonas putida E23
-
x * 30280, deduced from gene sequence, x * 30300, SDS-PAGE
-
homodimer
-
alpha2, 2 * 34000, SDS-PAGE
tetramer
-
alpha4, 4 * 30000, SDS-PAGE
tetramer
Pseudomonas putida E23
-
alpha4, 4 * 30000, SDS-PAGE
-
homodimer
-
alpha2, 2 * 40000, SDS-PAGE
additional information
-
hydroxybutyrate dehydrogenase and 3-hydroxyisobutyrate dehydrogenase activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
powdered ammonium sulfate is added to the enzyme solution until it becomes slightly turbid, after 4 days crystallization is complete
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 7.3
-
-
286551
5.7 - 9.3
-
-
286551
7 - 11.5
-
-
286551
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
enzyme activity is not decreased during preincubation at 45C within 30 min, but preincubation at 55C in 3 min can significantly denaturate and deactivate the enzyme; stable at 45C for 30 min, about 40% activity after 3 min at 55C
695710
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 50 mM Tris-HCl buffer, pH 8.5, 2 mM EDTA, 2 mM DTT, 50% glycerol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
96fold purified at 4C by ammonium sulfate fractionation and gel filtration; ammonium sulfate precipitation, hydrophobic interaction chromatography (Phenyl-Sepharose), anion exchange chromatography; native enzyme 100fold by ammonium sulfate fractionation, and hydrophobic interaction and anion exchange chromatography
-
affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 (DE3); MmsB gene, overexpression in Escherichia coli strain BL21, subcloning in strain DH5alpha; pEB81 recombinant vector introduced into Escherichia coli BL21 to overexpress 3-HIBADH protein
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HIBADH is downregulated in low-motility sperm, and is enriched expressed during human spermiogenesis
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D33R
-
higher affinity to cofactor NADP+ than to natural cofactor NAD+
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
3-HIBADH may play a role in biosynthesis of 3-hydroxypropionate as a biological source
additional information
Bacillus cereus ATCC 14579, Bacillus cereus ATCC14579
-
3-HIBADH may play a role in biosynthesis of 3-hydroxypropionate as a biological source
-