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Literature summary extracted from

  • Coelho, C.; Mahro, M.; Trincao, J.; Carvalho, A.T.; Ramos, M.J.; Terao, M.; Garattini, E.; Leimkuehler, S.; Romao, M.J.
    The first mammalian aldehyde oxidase crystal structure: insights into substrate specificity (2012), J. Biol. Chem., 287, 40690-40702.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.2.3.1 to 2.9 A resolution, used for elucidation of putative reaction mechanism of aldehyde oxidases Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
1.2.3.1 A807V does not affect the kinetic constants with smaller substrates like benzaldehyde or phthalazine, but affinity for bulkier substrates like phenanthridine decreases, whereas the catalytic efficiency is slightly raised Mus musculus
1.2.3.1 E1266Q complete loss of activity with different N-heterocyclic compounds as substrates, 60% reduction of enzyme activity with benzaldehyde Mus musculus
1.2.3.1 K889H 2–3fold decrease in the catalytic efficiency using benzaldehyde and phthalazine as substrates, but the Km-values remain the same Mus musculus
1.2.3.1 Y885M kinetic constants remain mainly the same with small hydrophobic substrates like benzaldehyde and phthalazine, bulkier substrates like phenanthridine or more charged substrates like N1-methylnicotinamide are converted with higher efficiency Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.2.3.1 benzamidine
-
Mus musculus
1.2.3.1 menadione
-
Mus musculus
1.2.3.1 norharmane
-
Mus musculus
1.2.3.1 raloxifene
-
Mus musculus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.2.3.1 additional information
-
additional information further kinetic parameters of phthalazine-DCPIP reaction in the absence or presence of the inhibitors benzamidine, menadione, norharmane, and raloxifene available in the publication Mus musculus
1.2.3.1 0.0011
-
Phthalazine K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0014
-
Phthalazine mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0023
-
benzaldehyde K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0025
-
benzaldehyde mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0027
-
Phthalazine A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0029
-
benzaldehyde A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0029
-
Phthalazine A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0032
-
Phthalazine Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0046
-
benzaldehyde A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0063
-
benzaldehyde Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0118
-
phenanthridine A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0161
-
phenanthridine K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0255
-
N1-methylnicotinamide K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0323
-
phenanthridine mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0334
-
phenanthridine Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0359
-
N1-methylnicotinamide A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0827
-
N1-methylnicotinamide Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0863
-
benzaldehyde E1266Q mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.1234
-
N1-methylnicotinamide A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.1285
-
N1-methylnicotinamide mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.1495
-
phenanthridine A807V mutant, pH 8.0, 37°C Mus musculus

Organism

EC Number Organism UniProt Comment Textmining
1.2.3.1 Mus musculus G3X982
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.2.3.1 mAOX3 purified from CD1 mouse liver as well as from a heterologous expression system from Escherichia coli, recombinant mAOX3 expressed as an N-terminal fusion protein with a His6 tag Mus musculus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.2.3.1 liver
-
Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.2.3.1 benzaldehyde + 2,6-dichlorophenol indophenol natural electron acceptor of enzyme is molecular oxygen, DCPIP i.e., 2,6-dichlorophenol indophenol Mus musculus ?
-
?
1.2.3.1 N1-methylnicotinamide + 2,6-dichlorophenol indophenol natural electron acceptor of enzyme is molecular oxygen, DCPIP i.e., 2,6-dichlorophenol indophenol Mus musculus ?
-
?
1.2.3.1 phenanthridine + H2O + O2
-
Mus musculus ?
-
?
1.2.3.1 phthalazine + 2,6-dichlorophenol indophenol natural electron acceptor of enzyme is molecular oxygen, DCPIP i.e., 2,6-dichlorophenol indophenol Mus musculus ?
-
?

Subunits

EC Number Subunits Comment Organism
1.2.3.1 homodimer each monomer comprises 1335 residues and can be divided into three major domains, a small 20000 Da N-terminal domain that harbors the two FeS clusters and connects to the 40000 Da FAD binding domain and finally the C-terminal 90000 Da domain containing the Moco binding site, with the molybdenum catalytic center Mus musculus

Synonyms

EC Number Synonyms Comment Organism
1.2.3.1 AOX3
-
Mus musculus
1.2.3.1 mAOX3
-
Mus musculus
1.2.3.1 mouse liver aldehyde oxidase 3
-
Mus musculus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.2.3.1 additional information
-
additional information further kinetic parameters of phthalazine-DCPIP reaction in the absence or presence of the inhibitors benzamidine, menadione, norharmane, and raloxifene available in the publication Mus musculus
1.2.3.1 0.052
-
N1-methylnicotinamide K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.17
-
benzaldehyde E1266Q mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.187
-
N1-methylnicotinamide A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.197
-
Phthalazine K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.245
-
N1-methylnicotinamide mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.32
-
benzaldehyde K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.39
-
N1-methylnicotinamide Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.45
-
N1-methylnicotinamide A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.683
-
benzaldehyde A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.685
-
Phthalazine A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.685
-
Phthalazine mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.69
-
Phthalazine A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.698
-
benzaldehyde mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.727
-
benzaldehyde A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.815
-
Phthalazine Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 0.862
-
phenanthridine mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 0.957
-
benzaldehyde Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 1.33
-
phenanthridine K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 3.63
-
phenanthridine A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 4.45
-
phenanthridine Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 5.25
-
phenanthridine A807V mutant, pH 8.0, 37°C Mus musculus

Cofactor

EC Number Cofactor Comment Organism Structure
1.2.3.1 FAD
-
Mus musculus
1.2.3.1 iron-sulfur centre two centers, FeSI and FeSII Mus musculus
1.2.3.1 molybdenum cofactor
-
Mus musculus

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.2.3.1 0.00125
-
menadione uncompetitive inhibition of phthalazine-2,6-dichlorophenol indophenol reaction, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0122
-
raloxifene competitive inhibition of phthalazine-2,6-dichlorophenol indophenol reaction, pH 8.0, 37°C Mus musculus
1.2.3.1 0.018
-
norharmane competitive inhibition of phthalazine-2,6-dichlorophenol indophenol reaction, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0225
-
benzamidine competitive inhibition of phthalazine-2,6-dichlorophenol indophenol reaction, pH 8.0, 37°C Mus musculus
1.2.3.1 0.0591
-
raloxifene uncompetitive inhibition of phthalazine-2,6-dichlorophenol indophenol reaction, pH 8.0, 37°C Mus musculus

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1.2.3.1 1.52
-
N1-methylnicotinamide A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 1.92
-
N1-methylnicotinamide mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 1.97
-
benzaldehyde E1266Q mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 2
-
N1-methylnicotinamide K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 4.72
-
N1-methylnicotinamide Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 12.5
-
N1-methylnicotinamide A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 26.7
-
phenanthridine mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 35.2
-
phenanthridine A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 82.8
-
phenanthridine K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 133.2
-
phenanthridine Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 136.7
-
benzaldehyde K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 151.8
-
benzaldehyde Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 158
-
benzaldehyde A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 175.5
-
Phthalazine K889H mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 235.7
-
benzaldehyde A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 238
-
Phthalazine A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 253.7
-
Phthalazine A807V mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 254.7
-
Phthalazine Y885M mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 279.3
-
benzaldehyde mAOX3 wild type, pH 8.0, 37°C Mus musculus
1.2.3.1 307.8
-
phenanthridine A807V/Y885M double mutant, pH 8.0, 37°C Mus musculus
1.2.3.1 489.3
-
Phthalazine mAOX3 wild type, pH 8.0, 37°C Mus musculus