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Information on EC 1.2.1.5 - aldehyde dehydrogenase [NAD(P)+] and Organism(s) Homo sapiens and UniProt Accession P47895
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1.2.1.5 aldehyde dehydrogenase [NAD(P)+]Specify your search results
Word Map
- 1.2.1.5
-
aldhs
-
retinoic
- disulfiram
-
alcohol-induced
- benzaldehyde
-
nadp+-dependent
- retinaldehyde
- cyanamide
-
meta-cleavage
-
aldh2*2
- phosphotransacetylase
-
1.2.1.3
-
hangover
-
alcohol-related
- medicine
- energy production
- synthesis
- analysis
- degradation
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Synonyms
acetaldehyde dehydrogenase, aldh3, aldh1a, myo-inositol dehydrogenase, class 3 aldehyde dehydrogenase, aldh9, tumor-associated aldehyde dehydrogenase, aldh2a, bcaldh, osaldh7, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Aldh1a3
ALDH
ALDH3
ALDHIII
-
-
-
-
BCP54
-
-
-
-
Corneal 15.8 kDa protein
-
-
-
-
Corneal protein 54
-
-
-
-
dehydrogenase, aldehyde (nicotinamide adenine dinucleotide (phosphate))
-
-
-
-
HTC-ALDH
-
-
-
-
Transparentin
-
-
-
-
Tumor-associated aldehyde dehydrogenase
-
-
-
-
ALDH
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-
SYSTEMATIC NAME
IUBMB Comments
aldehyde:NAD(P)+ oxidoreductase
-
CAS REGISTRY NUMBER
COMMENTARY
9028-88-0
-
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
3,4-dihydroxyphenylacetaldehyde + NAD+ + H2O
3,4-dihydroxyphenylacetate + NADH + H+
-
-
-
?
3,4-dihydroxyphenylglycolaldehyde + NAD+ + H2O
3,4-dihydroxyphenylglycolate + NADH + H+
-
-
-
?
retinal + NAD+ + H2O
retinoic acid + NADH + H+
preferred substrate of isozyme ALDH1A3
-
-
?
1-formyl-6-methylpyrene + NADP+ + H2O
6-methylpyrene-1-carboxylic acid + NADPH + H+
-
-
-
?
1-formyl-8-methylpyrene + NADP+ + H2O
8-methylpyrene-1-carboxylic acid + NADPH + H+
-
-
-
?
1-formylpyrene + NADP+ + H2O
pyrene-1-carboxylic acid + NADPH + H+
-
-
-
?
2-formylpyrene + NADP+ + H2O
pyrene-2-carboxylic acid + NADPH + H+
-
-
-
?
3,4-dihydroxyphenylacetaldehyde + NAD+ + H2O
3,4-dihydroxyphenylacetate + NADH + H+
-
-
-
?
3,4-dihydroxyphenylglycolaldehyde + NAD+ + H2O
3,4-dihydroxyphenylglycolate + NADH + H+
-
-
-
?
4-formylpyrene + NADP+ + H2O
pyrene-4-carboxylic acid + NADPH + H+
-
-
-
?
4-pyridinecarboxaldehyde + NAD+ + H2O
4-pyridinecarboxylate + NADH + H+
-
-
-
-
?
6-methoxy-2-naphthaldehyde + NADH + H+
(6-methoxynaphthalen-2-yl)methanol + NAD+
-
-
-
?
aldophosphamide + NAD+
N,N-bis-(2-chloroethyl)-diaminophosphoric-(2-carboxyethylester) + ?
-
-
-
-
?
p-hydroxybenzaldehyde + NADP+ + H2O
p-hydroxybenzoic acid + NADPH + H+
-
-
-
?
propanal + 1,N6-ethenoadenine dinucleotide
propionate + ?
-
isoenzyme E1 and E2
-
-
?
propanal + 3-acetylpyridine adenine dinucleotide
propionate + ?
-
isoenzyme E1 and E2
-
-
?
propanal + 3-pyridine adenine dinucleotide
propionate + ?
-
isoenzyme E1 and E2
-
-
?
propanal + beta-NADP+ + H2O
propionate + beta-NADPH + H+
-
isoenzyme E1 and E2
-
-
?
propanal + oxidized nicotinamide hypoxanthine dinucleotide + H2O
propionate + reduced nicotinamide hypoxanthine dinucleotide
-
isoenzyme E1 and E2
-
-
?
propionaldehyde + 3-pyridinealdehyde adenine dinucleotide + H2O
propionate + reduced 3-pyridinealdehyde adenine dinucleotide + H+
-
-
-
-
r
propionaldehyde + N-1,N6-ethenoadenine dinucleotide + H2O
propionate + reduced N-1,N6-ethenoadenine dinucleotide + H+
-
-
-
-
?
acetaldehyde + NAD+ + H2O
acetate + NADH + H+
-
activity with the enzyme from stomach mucosa, no activity with the enzyme from breast adenocarcinoma cell line
-
-
?
propanal + 3-thionicotinamide adenine dinucleotide
propionate + ?
-
isoenzyme E1
-
-
?
propanal + 3-thionicotinamide adenine dinucleotide
propionate + ?
-
no reaction with isoenzyme E2
-
-
?
additional information
?
-
-
enzyme plays a dual role in the absorption of UVR and in the oxidation of peroxidic aldehydes in the mammalian cornea
-
-
?
additional information
?
-
enzyme follows a sequential mode of reaction mechanism
-
-
?
additional information
?
-
ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH, product identification by thin layer chromatography (TLC)
-
-
-
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
additional information
?
-
-
enzyme plays a dual role in the absorption of UVR and in the oxidation of peroxidic aldehydes in the mammalian cornea
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,3,5-trimethyl-6-propyl-7H-furo[3,2-g][1]benzopyran-7-one
13.7% inhibition at 0.01 mM
-
2,3-dimethyl-5-propyl-7H-furo[3,2-g][1]benzopyran-7-one
19.6% inhibition at 0.01 mM
-
2-[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]acetamide
32.9% inhibition at 0.01 mM
-
2-[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]propanoic acid
6.1% inhibition at 0.01 mM
-
3,4,10-trimethyl-2H,6H-benzo[1,2-b:5,4-b']dipyran-2,6-dione
20.8% inhibition at 0.01 mM
-
3-benzyl-4-methyl-2-oxo-2H-1-benzopyran-7-yl methanesulfonate
13.1% inhibition at 0.01 mM
-
3-tert-butyl-5,6-dimethyl-7H-furo[3,2-g][1]benzopyran-7-one
13.0% inhibition at 0.01 mM
-
4-methyl-7-(2-oxo-2-phenylethoxy)-2H-1-benzopyran-2-one
32.9% inhibition at 0.01 mM
-
4-methyl-7-(2-oxopropoxy)-2H-1-benzopyran-2-one
35.9% inhibition at 0.01 mM
-
4-methyl-7-[(3-methylbut-2-en-1-yl)oxy]-2H-1-benzopyran-2-one
76.4% inhibition at 0.01 mM
-
4-methyl-7-[(prop-2-en-1-yl)oxy]-2H-1-benzopyran-2-one
90.5% inhibition at 0.01 mM
-
5-benzyl-2,3-dimethyl-7H-furo[3,2-g][1]benzopyran-7-one
18.4% inhibition at 0.01 mM
-
6-bromo-3-[(1E)-N-hydroxyethanimidoyl]-2H-1-benzopyran-2-one
8.3% inhibition at 0.01 mM
-
6-methyl-3,4-dihydro-2H,8H-benzo[1,2-b:5,4-b']dipyran-2,8-dione
46.4% inhibition at 0.01 mM
-
8,9-dimethyl-2,3-dihydrocyclopenta[c]furo[3,2-g][1]benzopyran-4(1H)-one
12.9% inhibition at 0.01 mM
-
9,10-dimethyl-1,2,3,4-tetrahydro-5H-6,8-dioxacyclopenta[b]phenanthren-5-one
5.9% inhibition at 0.01 mM
-
9,10-dimethyl-5H-6,8-dioxacyclopenta[b]phenanthren-5-one
6.6% inhibition at 0.01 mM
-
dimethyl ampal thiolester
complete inhibition of isozyme ALDH3 at 0.0075 mM
N-(2-(trifluoromethyl)benzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide
5.74% inhibition at 0.01 mM, pH 7.5, 25°C
-
N-(2-chlorobenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide
6.05% inhibition at 0.01 mM, pH 7.5, 25°C
-
N-(2-methylbenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide
5.26% inhibition at 0.01 mM, pH 7.5, 25°C
-
N-(3-methylbenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide
9.09% inhibition at 0.01 mM, pH 7.5, 25°C
-
N-benzyl-3-(2,3,5-trimethyl-7-oxo-7H-furo[3,2-g][1]benzopyran-6-yl)propanamide
31.7% inhibition at 0.01 mM
-
[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]acetonitrile
79.6% inhibition at 0.01 mM
-
3-thionicotinamide adenine dinucleotide
-
strong inhibition versus beta-NAD+, isoenzyme E2
6-benzyl-3,5-dimethyl-7H-furo[3,2-g][1]benzopyran-7-one
11.1% inhibition at 0.01 mM
-
6-benzyl-3,5-dimethyl-7H-furo[3,2-g][1]benzopyran-7-one
9.7% inhibition at 0.01 mM
-
additional information
design, synthesis of 1,3-dimethylpyrimidine-2,4-diones as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1, EC 1.2.1.36) inhibitors and comparison of inhibitory activities on different ALDH isozymes, overview. Poor inhibition by N-(2-fluorobenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide, N-(3-fluorobenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide, N-(3-chlorobenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide, N-(3-(trifluoromethyl)benzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide, N-(2-methoxybenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide, N-(3-methoxybenzyl)-N-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-3-(4-(4-isopropylbenzoyl)piperazin-1-yl)propanamide, and CM026
-
additional information
inhibition of the aldehyde dehydrogenase 1/2 family by psoralen and coumarin derivatives, structure-function relationships, overview. 3,5-dimethyl-6-propyl-7H-furo[3,2-g][1]benzopyran-7-one, 2,3,5,6-tetramethyl-7H-furo[3,2-g][1]benzopyran-7-one, methyl 2-[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]propanoate, 2,3,5,6,9-pentamethyl-7H-furo[3,2-g][1]benzopyran-7-one, 3,4-dimethyl-6,7,8,9-tetrahydro-2H-[1]benzofuro[3,2-g][1]benzopyran-2-one, 2,3,5-trimethyl-6-[3-oxo-3-(piperidin-1-yl)propyl]-7H-furo[3,2-g][1]benzopyran-7-one, 5-methyl-2-[(3-oxobutan-2-yl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one, 7-(2-oxopropoxy)-2H-1-benzopyran-2-one, 3,4,8,9-tetramethyl-7H-furo[2,3-f][1]benzopyran-7-one, 2-[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]-N-phenylacetamide, 7-(diethylamino)-4-methyl-2H-1-benzopyran-2-one, 3-[(3-oxobutan-2-yl)oxy]-6H-dibenzo[b,d]pyran-6-one, 3-(7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-yl)propanoic acid, and N-(4,7-dimethyl-2-oxo-2H-1-benzopyran-6-yl)-2-methylpropanamide are inactive as inhibitors
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
3,4-dihydroxyphenylacetaldehyde
isozyme ALDH2 from liver
0.0042
3,4-dihydroxyphenylacetaldehyde
isozyme ALDH1A1 from brain
0.091
4-Pyridinecarboxaldehyde
-
reaction with NAD+ or NADP+, enzyme from breast adenocarcinoma cell line
0.19
4-Pyridinecarboxaldehyde
-
reaction with NAD+ or NADP+, enzyme from stomach mucosa
0.64
benzaldehyde
-
reaction with NAD+ or NADP+, enzyme from breast adenocarcinoma cell line
0.013
Chloroacetaldehyde
-
mutant enzyme T244S, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.039
Chloroacetaldehyde
-
wild type enzyme, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.052
Chloroacetaldehyde
-
mutant enzyme T244G, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.3
Chloroacetaldehyde
-
mutant enzyme T244A, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.46
Chloroacetaldehyde
-
mutant enzyme T244V, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.048
NAD+
-
wild type enzyme, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.094
NAD+
-
mutant enzyme T244S, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.19
NAD+
-
mutant enzyme T244G, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.39
NAD+
-
mutant enzyme T244V, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
2.1
NAD+
-
mutant enzyme T244A, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.067
octanal
-
reaction with NAD+ or NADP+, enzyme from breast adenocarcinoma cell line
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.47
Chloroacetaldehyde
-
mutant enzyme T244S, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.63
Chloroacetaldehyde
-
mutant enzyme T244G, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
2.5
Chloroacetaldehyde
-
mutant enzyme T244V, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
4
Chloroacetaldehyde
-
mutant enzyme T244A, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
7.7
Chloroacetaldehyde
-
wild type enzyme, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.47
NAD+
-
mutant enzyme T244S, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
0.63
NAD+
-
mutant enzyme T244G, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
2.5
NAD+
-
mutant enzyme T244V, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
4
NAD+
-
mutant enzyme T244A, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
7.7
NAD+
-
wild type enzyme, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.5
Chloroacetaldehyde
-
mutant enzyme T244V, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
12.2
Chloroacetaldehyde
-
mutant enzyme T244G, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
13.2
Chloroacetaldehyde
-
mutant enzyme T244A, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
183.3
Chloroacetaldehyde
-
mutant enzyme T244S, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
200
Chloroacetaldehyde
-
wild type enzyme, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
1.8
NAD+
-
mutant enzyme T244A, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
3.3
NAD+
-
mutant enzyme T244G, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
6.5
NAD+
-
mutant enzyme T244V, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
33.3
NAD+
-
mutant enzyme T244S, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
158.3
NAD+
-
wild type enzyme, in 25 mM Na-HEPES buffer (pH 7.4), temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
exhibiting oxazaphosphorine-specific acquired resistance, enzyme form ALDH3
additional information
ALDH3A1 is highly expressed in lung carcinoma cell line A549 and EKVX, as well as in the large cell carcinoma cell line H460. Isozyme ALDH1A1 (EC 1.2.1.36) shows a similar expression pattern like ALDH3A1. Other members of the aldehyde dehydrogenase family are not expressed in the lung cancer cell lines examined
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
aldehyde dehydrogenase 1A1 (ALDH3A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD(P)+ to NAD(P)H
metabolism
ALDH1A1 and ALDH3A1 have the same GSH/DHLA-dependent NAD+-reduction activity
physiological function
physiological function
-
isotype ALDH1A1 is the key ALDH isozyme linked to tissue stem cells populations and an important contributor to cancer stem cells function in cancers
physiological function
aldehyde dehydrogenase 3A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD+ reduction. ALDH3A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket. It is thus a distinct biochemical reaction from the classic aldehyde-dehydrogenase activity catalyzed by ALDH3A1. The GSH/DHLA-dependent NAD+-reduction activity of ALDH3A1 can decrease cellular NAD+/NADH ratio and promote tumor growth
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AL1A3_HUMAN
512
0
56108
Swiss-Prot
Secretory Pathway (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the apoenzyme is crystallized by using 100 mM ACES, pH 6.4, 100-200 mM guanidine-HCl, 1-10 mM MgCl2 and 1617% (w/v) PEG 6000, the mutant T244A in complex with NAD is crystallized by using 100 mM ACES, pH 6.4, 100 mM guanidineHCl, 10 mM MgCl2 and 18% (w/v) PEG 6000
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T186S
the mutant has increased activity against aldehyde and decreased activity against smaller substrates like benzaldehyde compared to the native enzyme and cells transformed with the point mutant are better protected against the killing effect of cyclophosphamides
T244A
-
the mutant exhibits reduced catalytic efficiency toward substrate and coenzyme
T244G
-
the mutant exhibits reduced catalytic efficiency toward substrate and coenzyme
T244S
-
the mutant exhibits reduced catalytic efficiency toward substrate and coenzyme
T244V
-
the mutant exhibits reduced catalytic efficiency toward substrate and coenzyme
additional information
simultaneous knockout of ALDH1A1 (EC 1.2.1.36) and its isozyme ALDH3A1 in lung cancer cell line NCI-H460 inhibits tumor growth in a xenograft model. Moreover, the ALDH1A1 mutants that retain their GSH/DHLA-dependent NAD+ reduction activity and lose their aldehyde-dehydrogenase activity are able to decrease the NAD+/NADH ratio and to rescue the impaired growth of ALDH1A1/3A1 double knockout tumor cells
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
the activity at a physiological pH value (7.4) is nearly 50% of the activity observed at the optimal pH value
684721
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
freezing and thawing, more than once causes complete loss of activity of enzyme from breast adenocarcinoma cell line, enzyme from stomach mucosa retains 40% of its activity even after being frozen and thawed eight times
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, pH 7.5, 25 mM sodium phosphate supplemented with 1 mM EDTA and 0.05% dithiothreitol, 10% glycerol, enzyme from breast adenocarcinoma cell line completely loses activity after 15 days, enzyme from stomach mucosa loses 75% of its activity after 3 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
DEAE-cellulose column chromatography, 5-AMP Sepharose 4B and 4-hydroxyacetophenone affinity chromatography
-
purification of the enzyme(s) responsible for the GSH/DHLA-dependent NAD+ reduction activity from large-scale cell cultures, native enzyme from EKVX lung cancer cells by ultracentrifugation of crude cell extract and anion echange chromatography, hydrophobic interaction and hydroxyapatite chromatography, followed by gel filtration and another different step of anion exchange chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
aldehyde dehydrogenase 1A3 is transcriptionally activated by 0.001 mM all-trans-retinoic acid in human epidermal keratinocytes whereas no upregulation is detected in dermal fibroblasts and HeLa cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
19 ALDH genes are identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, gamma-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. ALDH enzymes display multiple catalytic and non-catalytic functions including ester hydrolysis, antioxidant properties, xenobiotic bioactivation and UV light absorption
medicine
-
high ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Izaguirre, G.; Pietruszko, R.; Cho, S.; MacKerell, A.D., Jr.
Human aldehyde dehydrogenase catalytic activity and structural interactions with coenzyme analogs
J. Biomol. Struct. Dyn.
19
429-447
2001
Homo sapiens
King, G.; Holmes, R.S.
Human corneal aldehyde dehydrogenase: purification, kinetic characterisation and phenotypic variation
Biochem. Mol. Biol. Int.
31
49-63
1993
Homo sapiens
Sreerama, L.; Sladek, N.E.
Identification and characterization of a novel class 3 aldehyde dehydrogenase overexpressed in a human breast adenocarcinoma cell line exhibiting oxazaphosphorine-specific acquired resistance
Biochem. Pharmacol.
45
2487-2505
1993
Homo sapiens
Glatt, H.; Rost, K.; Frank, H.; Seidel, A.; Kollock, R.
Detoxification of promutagenic aldehydes derived from methylpyrenes by human aldehyde dehydrogenases ALDH2 and ALDH3A1
Arch. Biochem. Biophys.
477
196-205
2008
Homo sapiens (P30838)
Ho, K.K.; Mukhopadhyay, A.; Li, Y.F.; Mukhopadhyay, S.; Weiner, H.
A point mutation produced a class 3 aldehyde dehydrogenase with increased protective ability against the killing effect of cyclophosphamide
Biochem. Pharmacol.
76
690-696
2008
Homo sapiens (P30838), Homo sapiens
Quash, G.; Fournet, G.; Courvoisier, C.; Martinez, R.M.; Chantepie, J.; Paret, M.J.; Pharaboz, J.; Joly-Pharaboz, M.O.; Gore, J.; Andre, J.; Reichert, U.
Aldehyde dehydrogenase inhibitors: alpha,beta-acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but irreversible apoptogens for cancer epithelial cells from human prostate in culture
Eur. J. Med. Chem.
43
906-916
2008
Homo sapiens (P30838), Homo sapiens
Marchitti, S.A.; Deitrich, R.A.; Vasiliou, V.
Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase
Pharmacol. Rev.
59
125-150
2007
Homo sapiens (P30838), Homo sapiens (P43353), Homo sapiens (P47895)
Marchitti, S.A.; Brocker, C.; Stagos, D.; Vasiliou, V.
Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily
Expert. Opin. Drug Metab. Toxicol.
4
697-720
2008
Homo sapiens
Koenig, U.; Amatschek, S.; Mildner, M.; Eckhart, L.; Tschachler, E.
Aldehyde dehydrogenase 1A3 is transcriptionally activated by all-trans-retinoic acid in human epidermal keratinocytes
Biochem. Biophys. Res. Commun.
400
207-211
2010
Homo sapiens (P47895)
Gonzalez-Segura, L.; Ho, K.K.; Perez-Miller, S.; Weiner, H.; Hurley, T.D.
Catalytic contribution of threonine 244 in human ALDH2
Chem. Biol. Interact.
202
32-40
2013
Homo sapiens
Alam, M.F.; Laskar, A.A.; Choudhary, H.H.; Younus, H.
Human salivary aldehyde dehydrogenase: purification, kinetic characterization and effect of ethanol, hydrogen peroxide and sodium dodecyl sulfate on the activity of the enzyme
Cell Biochem. Biophys.
74
307-315
2016
Homo sapiens (P30838)
Tomita, H.; Tanaka, K.; Tanaka, T.; Hara, A.
Aldehyde dehydrogenase 1A1 in stem cells and cancer
Oncotarget
7
11018-11032
2016
Homo sapiens
Ma, Z.; Jiang, L.; Li, G.; Liang, D.; Li, L.; Liu, L.; Jiang, C.
Design, synthesis of 1,3-dimethylpyrimidine-2,4-diones as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity
Bioorg. Chem.
101
103971
2020
Homo sapiens (P30838)
Buchman, C.D.; Hurley, T.D.
Inhibition of the aldehyde dehydrogenase 1/2 family by psoralen and coumarin derivatives
J. Med. Chem.
60
2439-2455
2017
Homo sapiens (P30838)
Wang, B.; Chen, X.; Wang, Z.; Xiong, W.; Xu, T.; Zhao, X.; Cao, Y.; Guo, Y.; Li, L.; Chen, S.; Huang, S.; Wang, X.; Fang, M.; Shen, Z.
Aldehyde dehydrogenase 1A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD+ reduction
Oncotarget
8
67043-67055
2017
Homo sapiens (P30838)
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